10.1007/s11060-009-9953-x</TIT= LE> <META http-equiv=3DContent-Type content=3D"text/html; = charset=3DISO-8859-1"><LINK=20 href=3D"http://www.springerlink.com/config/css/A++_common.css" = type=3Dtext/css=20 rel=3DstyleSheet><LINK=20 href=3D"http://www.springerlink.com/config/css/content_A++_SpringerLink.c= ss"=20 type=3Dtext/css rel=3DstyleSheet> <META content=3D"MSHTML 6.00.6000.16850" name=3DGENERATOR></HEAD> <BODY class=3Dfor-print> <TABLE cellPadding=3D2 border=3D1> <TBODY> <TR class=3Dheader> <TD>Journal of Neuro-Oncology</TD></TR> <TR> <TD>=A9 The Author(s) 2009</TD></TR> <TR> <TD>10.1007/s11060-009-9953-x</TD></TR></TBODY></TABLE> <H2 class=3Drubric>Clinical Study - Patient Study</H2> <DIV class=3DHeading1><A name=3Dtitle></A>[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-Methionine = positron=20 emission tomography in the management of children and young adults with = brain=20 tumors </DIV> Norbert Galldiks1 <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#ContactOfAuthor1"><IMG=20 alt=3D"Contact Information"=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/contact.gif" = border=3D0></A>, Lutz W. Kracht2,=20 Frank Berthold3, Hrvoje Miletic4,=20 Johannes C. Klein2, 7, Karl Herholz2, = 5,=20 Andreas H. Jacobs2, 6 and=20 Wolf-Dieter Heiss2 <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff1></A>(1) </TD> <TD>Department of Neurology, University of = Cologne, Kerpener Str. 62, 50924 Cologne,=20 Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff2></A>(2) </TD> <TD>Max Planck-Institute for Neurological=20 Research, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff3></A>(3) </TD> <TD>Department of Paediatric Oncology, = University=20 of Cologne, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff4></A>(4) </TD> <TD>Department of Neuropathology, = University of=20 Cologne, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff5></A>(5) </TD> <TD>Present address: Wolfson = Molecular=20 Imaging Centre, University of Manchester, Manchester,=20 UK</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff6></A>(6) </TD> <TD>Present address: Department of=20 Neurology, Klinikum Fulda, = Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff7></A>(7) </TD> <TD>Present address: Department of=20 Neurology, University of Frankfurt, Frankfurt,=20 Germany</TD></TR></TBODY></TABLE> <A name=3DContactOfAuthor1></A> <TABLE class=3DContact> <TBODY> <TR> <TD vAlign=3Dtop><IMG alt=3D"Contact Information"=20 = src=3D"http://www.springerlink.com/content/w74xq54758322wm2/contact.gif" = border=3D0></TD> = <TD>Norbert Galldiks</STRO= NG> Email:=20 <A=20 = href=3D"mailto:Norbert.Galldiks@uk-koeln.de">Norbert.Galldiks@uk-koeln.de= </A></TD></TR></TBODY></TABLE> Received:=20 4 March 2009 Accepted:=20 22 June 2009 Published online:=20 4 July 2009 <DIV class=3DAbstract><A name=3DAbs1></A><SPAN=20 class=3DAbstractHeading>Abstract Only a few=20 Methyl-[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-methionine = (MET)=20 positron emission tomography (PET) studies have focused on children and = young=20 adults with brain neoplasm. Due to radiation exposure, long scan = acquisition=20 time, and the need for sedation in young children MET-PET studies should = be=20 restricted to this group of patients when a decision for further therapy = is not=20 possible from routine diagnostic procedures alone, e.g., structural = imaging. We=20 investigated the diagnostic accuracy of MET-PET for the differentiation = between=20 tumorous and non-tumorous lesions in this group of patients. Forty eight = MET-PET=20 scans from 39 patients aged from 2 to 21 years (mean=20 15 =B1 5.0 years) were analyzed. The MET tumor-uptake = relative to a=20 corresponding control region was calculated. A receiver operating = characteristic=20 (ROC) was performed to determine the MET-uptake value that best = distinguishes=20 tumorous from non-tumorous brain lesions. A differentiation between = tumorous=20 (n =3D 39) and non-tumorous brain lesions=20 (n =3D 9) was possible at a threshold of 1.48 of = relative=20 MET-uptake with a sensitivity of 83% and a specificity of 92%, = respectively. A=20 differentiation between high grade malignant lesions (mean=20 MET-uptake =3D 2.00 =B1 0.46) and low grade tumors = (mean=20 MET-uptake =3D 1.84 =B1 0.31) was not possible. = There was a=20 significant difference in MET-uptake between the histologically = homogeneous=20 subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO = grade III=20 (P =3D 0.02). MET-PET might be a useful tool to = differentiate=20 tumorous from non-tumorous lesions in children and young adults when a = decision=20 for further therapy is difficult or impossible from routine structural = imaging=20 procedures alone. </DIV> Keywords Brain=20 tumor - Children - PET - Methionine -&= nbsp;Molecular=20 imaging <DIV class=3DArticleNote>Norbert Galldiks and Lutz W. = Kracht have=20 contributed equally to this work.</DIV> <DIV class=3D""><A name=3DSec1></A> <HR> <DIV class=3Dheading2>Introduction</DIV> Methyl-[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-methionine = (MET)=20 positron emission tomography (PET) is a well established method in the = diagnosis=20 and management of adult patients suffering from brain tumors. Besides = less=20 common tumors of the cranial cavity (e.g., embryogenic tumors, = glioneural=20 tumors, lymphomas, meningiomas) MET is incorporated into malignant = gliomas=20 (e.g., anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic=20 oligodendroglioma, glioblastoma multiforme), even in low grade gliomas = (e.g.,=20 WHO-grade II astrocytoma), and it is employed in the management of these = patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>].=20 MET is a sensitive tracer in tumor detection. In adults, it = differentiates=20 benign from malignant lesions with high sensitivity and specificity with = comparatively low background activity in normal brain tissue [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>].=20 MET-uptake correlates to cell proliferation in cell culture [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR3">3</A></CITE>],=20 Ki-67 expression [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR4">4</A></CITE>],=20 cell nuclear antigen expression [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR5">5</A></CITE>]=20 and microvessel density [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>],=20 indicating its role as a marker for active tumor proliferation and = angiogenesis.=20 In addition it seems to be useful in monitoring chemotherapy in patients = with=20 brain tumors [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR7">7</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR8">8</A></CITE>].=20 The main advantage of amino acid tracers when compared to=20 [18F]-2-fluoro-2-deoxy-<SPAN=20 style=3D"FONT-VARIANT: small-caps">d-glucose (FDG) = is the=20 excellent delineation of tumors extent [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR9">9</A></CITE>].=20 Despite this good imaging properties of MET-PET only a few = studies=20 have focused on children and young adults with brain neoplasms [<CITE><A = href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR10">10</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>].=20 Pirotte and co-workers provided evidence that MET- and FDG-PET improves = the=20 diagnostic yield in stereotactic brain biopsies and surgical management = of brain=20 tumors in children [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR11">11</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR13">13</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR14">14</A></CITE>].=20 In planning a PET scan for a child, various aspects need=20 consideration. For practical use and implementation of PET in children = see=20 Borgwardt et al. [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR15">15</A></CITE>].=20 Because molecular imaging can not replace structural imaging modalities = like=20 magnetic resonance imaging (MRI) or computed tomography (CT), it is = always a=20 supplementary investigation with radioactive exposure and comparatively = long=20 scan times. In respect of the effective radiation dose, whole-body = distribution=20 of FDG in children differed from adults: a greater proportion of the = injected=20 activity accumulated into the brain and less was excreted to urine = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR16">16</A></CITE>].=20 The dose of the injected radionuclide has to be adjusted for body = weight. In=20 addition, in children sedation or even general anesthesia especially in = very=20 young children is necessary to avoid patient movement. PET should be = restricted=20 to children with brain tumors where a clear decision for further therapy = planning is not possible from structural routine imaging alone. We investigated the diagnostic accuracy of MET-PET for the = differentiation between tumorous and non-tumorous lesions in this = selected group=20 of patients. </DIV> <DIV class=3D""><A name=3DSec2></A> <HR> <DIV class=3Dheading2>Patients and methods</DIV> <DIV class=3D""><A name=3DSec3></A> <DIV class=3DHeading3>Patients</DIV> Thirty-nine patients were included in the study. At the = time of=20 MET-PET investigation, the mean age of all patients was=20 15 =B1 5.0 years (range 2=9621 years). The patients = were=20 referred to the PET-unit of the Max-Planck-Institute for Neurological = Research=20 in Cologne, Germany because decision from MRI findings was difficult for = further=20 diagnostic procedures or therapy planning. A total of 48 MET-PET scans = were=20 performed for all patients. Two or more investigations were performed in = 6=20 patients during follow up. The purpose of the scan and potential risks = were=20 explained to the patients or their legal guardians before they gave = their=20 informed consent to the investigation. In order to differentiate between children and young = adults, the=20 threshold of age was set at 15 years. In the literature, a clear = definition=20 of a young adult was not available; therefore, the threshold of = 15 years=20 was set in the middle of the period of life between 10 and = 20 years, which=20 is the current definition of adolescence by the World Health = Organization (WHO).=20 In our collective, at the time of MET-PET imaging 17 patients were under = the age=20 of 15 years. To evaluate the diagnostic accuracy of MET-PET for the=20 differentiation between tumorous and non-tumorous lesions in this group = of=20 patients, routine diagnostic procedures like histological examinations = and=20 follow-up structural imaging (MRI or CT scans with contrast enhancing = agents)=20 were performed. Follow-up structural imaging was performed to confirm or = to=20 exclude a change of the lesion size over the course of the disease. = Structural=20 imaging procedures were performed within the clinical routine = periodically every=20 3=9612 months, depending on the WHO-grade of the brain tumor. E.g., = a=20 low-grade tumor was examined every 12 months, a WHO-grade IV tumor = was=20 examined every 3=966 months. Recurrence of a brain tumor was = defined=20 according to the Macdonald criteria (gadolinium enhancement or tumor = enlargement=20 ≥25%) [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR17">17</A></CITE>].=20 Furthermore, after clinical deterioration or occurrence of new symptoms, = structural imaging was performed promptly. After MET-PET imaging, the = mean=20 follow-up (imaging procedures like MRI or CT and/or clinically) was=20 25.5 =B1 43.3 months. Additionally, clinical aspects like = an=20 asymptomatic course of the disease, therapy response (e.g. = anticonvulsive=20 medication, corticosteroids) or a deterioration of symptoms were = considered as=20 well. <DIV class=3DPara> <DIV class=3D"">In all patients in which a tumorous lesion=20 (n =3D 31) was suspected (primary tumor or = recurrent/residual=20 tumor), the diagnosis was confirmed histologically during the course of = the=20 disease (Tables <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab1">1</A>,=20 <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab2">2</A>).=20 In patients with a non-tumorous lesion (n =3D 8), the = diagnosis=20 was confirmed histologically, clinically, by imaging results (MRI or CT = scan),=20 or clinically in combination with follow-up imaging results = (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab1></A> <DIV class=3DCapt>Table 1 Individual patient=20 data </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft> Newly diagnosed (ND)/recurrence (REC)</TH> <TH align=3Dleft> Sxa </TH> <TH align=3Dleft> Rxb </TH> <TH align=3Dleft> Cxc </TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right fronto- parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> 3rd ventricle</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Sellar region</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> DNT</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> DIG</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Right parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left precentral</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Quadrigeminal plate</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pleomorphic xanthoastrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 16</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Ependymoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 17</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 18</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 19</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left pericentral</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 20</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 21</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left temporo-parietal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 22</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right internal capsula</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 23</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 24</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 25</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 26</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 27</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Pons</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 28</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 29</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Ependymoblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right fronto-temporal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 30</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Brainstem</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 31</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right temporo-occipital</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 32</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 33</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 34</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Epilepsy</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 35</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pineal cyst</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Pineal gland</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 36</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ADEM</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 37</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left parieto-occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 38</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 39</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Stroke PCA</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Individual data of 39 children and young adults with = suspected=20 newly diagnosed or recurrent brain tumor who underwent = MET-PET</DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">DIG Desmoplastic infantile ganglioglioma, = DNT=20 dysembryoplastic neuroepithelial tumor, ATRT atypical teratoid = rhabdoid=20 tumor, ADEM acute demyelinating encephalomyelitis, PCA = posterior=20 cerebral artery </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">aSurgery before MET-PET </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">bRadiation therapy before MET-PET = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">cChemotherapy before MET-PET </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">dPatients were investigated at the time of = first=20 diagnosis and at the time of suspected recurrence </DIV></DIV></DIV><A=20 name=3DTab2></A> <DIV class=3DCapt>Table 2 Number = of patients=20 with tumors of different histological types and non-tumorous lesions = </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Histological diagnosis and WHO grade</TH> <TH align=3Dleft> Total</TH> <TH align=3Dleft> Under age of 15</TH> <TH align=3Dleft> 15=9621 years</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D4> Histological diagnoses</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pilocytic astrocytoma I</TD> <TD align=3Dleft> 6</TD> <TD align=3Dleft> 3</TD> <TD align=3Dleft> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma II</TD> <TD align=3Dleft> 6</TD> <TD align=3Dleft> 3</TD> <TD align=3Dleft> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pleomorphic xanthoastrocytoma II</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma III</TD> <TD align=3Dleft> 4</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Oligoastrocytoma III</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Glioblastoma IV</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Medulloblastoma IV</TD> <TD align=3Dleft> 4</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Atypical teratoid rhabdoid tumor IV</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoma II</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoblastoma IV</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> DNT I</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Desmoplastic infantile ganglioglioma I</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Non-tumor lesions</TD> <TD align=3Dleft> 8</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 8</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Total</TD> <TD align=3Dleft> 39</TD> <TD align=3Dleft> 17</TD> <TD align=3Dleft> 22</TD></TR></TBODY></TABLE></DIV></DIV> <DIV class=3DPara> <DIV class=3D"">In 16 MET-PET scans of 15 patients (5 patients under the = age of=20 15 years) a primary brain tumor was suspected on MRI (Table <A = href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab3">3</A>).=20 In these patients MET-PET was performed to confirm MRI findings and to = give=20 additional information about extent and dignity of the lesion.<A = name=3DTab3></A> <DIV class=3DCapt>Table 3 Patients = with a=20 suspected primary brain tumor on MRI </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> DNT</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> DIG</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Right parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Quadrigeminal plate</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 32</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 33</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 34</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Epilepsy</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 35</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pineal cyst</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Pineal gland</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 36</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ADEM</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right occipital</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 37</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left parieto-occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 38</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 39</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Stroke PCA</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">In these patients PET was performed to confirm MRI = findings and to=20 give additional information about extent and dignity of the lesion = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) or by = follow-up MRI or CT scans </DIV></DIV></DIV></DIV></DIV> Presence or absence of a primary tumor at the time of = MET-PET=20 imaging (n =3D 16 in 15 patients) was confirmed (i)=20 histologically after the MET-PET examination by surgery or stereotactic = biopsy=20 (n =3D 8), (ii) clinically (n =3D 4), = (iii) or by=20 follow-up MRI or CT scans (n =3D 3). <DIV class=3DPara> <DIV class=3D"">In 21 MET-PET scans of 20 patients (11 patients under = the age of=20 15 years) a recurrent or residual tumor was suspected after = therapy, but a=20 clear differentiation from posttherapeutic changes was not possible from = MRI=20 alone (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab4">4</A>).<A=20 name=3DTab4></A> <DIV class=3DCapt>Table 4 Patients = with=20 suspected recurrent tumor after therapy in which a clear differentiation = from=20 posttherapeutic changes was not possible from MRI alone </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> 3rd ventricle</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 3</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left thalamus</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Sellar region</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left frontal</TD> <TD align=3Dleft char=3D"."> </TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Ependymoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left pericentral</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 22</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right internal capsula</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 23</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 24</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 25</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 26</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 16</TD> <TD align=3Dchar char=3D"."> 27</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Pons</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 17</TD> <TD align=3Dchar char=3D"."> 28</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 18</TD> <TD align=3Dchar char=3D"."> 29</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Ependymoblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right fronto-temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 19</TD> <TD align=3Dchar char=3D"."> 30</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Brainstem</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 20</TD> <TD align=3Dchar char=3D"."> 31</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right temporo-occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) by = follow-up=20 MRI or CT scans, (4) or clinically in combination with follow-up imaging = results=20 </DIV></DIV></DIV></DIV></DIV> Presence or absence of a recurrent or residual tumor with = previously=20 histologically confirmed diagnosis at the time of MET-PET imaging=20 (n =3D 21 in 20 patients) was confirmed (i) by further=20 histological diagnosis after surgery or stereotactic biopsy=20 (n =3D 5), (ii) clinically (n =3D 2), = (iii) by=20 follow-up MRI or CT scans (n =3D 5), (iv) or clinically = in=20 combination with follow-up imaging results (n =3D 8). = <DIV class=3DPara> <DIV class=3D"">Additionally, 4 patients were examined initially when a = primary=20 brain tumor was suspected on MRI and, afterward, when a recurrent or = residual=20 tumor was suspected after therapy (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab5">5</A>).=20 In these 4 patients, 11 MET-PET scans were performed (one patient of = these 4=20 patients was under the age of 15 years).<A name=3DTab5></A> <DIV class=3DCapt>Table 5 Patients = with brain=20 tumor which were examined initially when a primary brain tumor was = suspected on=20 MRI and, afterward, when a recurrent or residual tumor was suspected = after=20 therapy </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left precentral</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 15</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pleomorphic xanthoastrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"."> 1,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left temporo-parietal</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4,1</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) by = follow-up=20 MRI or CT scans, (4) or clinically in combination with follow-up imaging = results=20 </DIV></DIV></DIV></DIV></DIV> Presence of primary tumor and recurrent or residual tumor, = respectively, was confirmed (i) both histologically = (n =3D 1),=20 (ii) clinically and histologically (n =3D 1), (iii) or = clinically=20 in combination with imaging results and histologically = (n =3D 2).=20 Most tumors were located in critical areas like basal = ganglia,=20 midbrain, and brainstem or next to motor areas in the pericentral region = or=20 speech relevant areas in the left temporal lobe. </DIV> <DIV class=3D""><A name=3DSec4></A> <DIV class=3DHeading3>Methods</DIV> Altogether, 48 MET-PET studies of the 39 patients were = performed=20 either on an ECAT EXACT HR or ECAT EXACT scanner (Siemens-CTI, = Knoxville, TN)=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR19">19</A></CITE>].=20 In one child a mild sedation and in four children a general anesthesia = was=20 necessary to avoid patient movement. In these cases, the children were = under the=20 age of 12 years. 11 MBq/kg bodyweight MET (maximum = 740 MBq) were=20 injected intravenously. MET was synthesized according to the method of = Berger et=20 al. [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR20">20</A></CITE>].=20 Tracer accumulation was recorded over 60 min directly after tracer=20 injection or over 40 min beginning 20 min after tracer = injection. The=20 entire brain was scanned in 47 transaxial slices. Summed activity from = 20 to=20 60 min after tracer injection was used for image reconstruction. = Scans were=20 corrected for attenuation and scatter. Spatial resolution was 6 mm = or=20 better in all dimensions. As described previously, a circular region of interest = (ROI) of=20 7 mm diameter was placed in the area of maximum MET-uptake = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 Mean uptake of this ROI was determined relative to a control region in = the=20 unaffected hemisphere which was obtained by mirroring the ROI along the = medial=20 sagittal plane. In midline or brainstem lesions the reference ROI was = placed in=20 the fronto-lateral cortex of the unaffected hemisphere. To determine the relative MET-uptake value that best = distinguishes=20 tumorous from non-tumorous brain lesions, a receiver operating = characteristic=20 (ROC) analysis was performed by varying the threshold of MET-uptake over = the=20 whole range of values and calculating sensitivity and specificity for = each=20 value. For statistical analyses, SPSS version 10.0.7 (SPSS Inc., = Chicago,=20 Illinois) was used. Graphs were plotted with SigmaPlot, version 7.0 = (SPSS Inc.,=20 Chicago, Illinois). </DIV></DIV> <DIV class=3D""><A name=3DSec5></A> <HR> <DIV class=3Dheading2>Results</DIV> <DIV class=3DPara> <DIV class=3D"">At a threshold of 1.48, relative MET-uptake = differentiation=20 between tumorous (n =3D 39) and non-tumorous brain = lesions=20 (n =3D 9) was possible with a sensitivity of 83% and = specificity=20 of 92% (area under the curve =3D 0.94, 95%-confidence=20 interval =3D 0.87=961.00; Fig. <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig1">1</A>).=20 At this threshold, 8 of 9 non-tumorous lesions were classified correctly = by=20 using MET-PET imaging. The false-positive case was one patient with a = newly=20 developed contrast enhancing lesion in the pons 14 years after = treatment of=20 a medulloblastoma with a MET-uptake of 1.53. This lesion disappeared = slowly=20 without treatment in follow-up MRI examinations 1 and 4 months = after the=20 PET investigation. At a threshold greater than 1.53, the specificity was = 100%=20 without false positive findings.=20 <DIV class=3DFigure><A name=3DFig1></A><IMG=20 alt=3DMediaObjects/11060_2009_9953_Fig1_HTML.gif=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/MediaObjects/= 11060_2009_9953_Fig1_HTML.gif"></DIV> <DIV class=3DCapt>Fig. 1 ROC = analysis of=20 relative [11C-MET]-uptake to differentiate tumor from = non-tumorous=20 lesions </DIV> <HR> </DIV></DIV> Thirty-four of 39 confirmed tumors were correctly = classified=20 positive. False negative findings included two pilocytic astrocytoma WHO = grade I=20 and two diffuse astrocytoma WHO grade II. In one child with a suspected=20 medulloblastoma, several small areas with a slight MET-uptake of 1.22 = were=20 observed. However, this uptake had to be classified as false negative, = because a=20 manifest tumor progression could be diagnosed 5 months later. At a threshold of 1.48, relative MET-uptake = differentiation between=20 tumorous and non-tumorous brain lesions was possible in the group of = patients=20 under the age of 15 years (n =3D 17) with a = sensitivity of=20 91% and a specificity of 100%. <DIV class=3DPara> <DIV class=3D"">The mean MET-uptake in 17 high grade tumors = [astrocytoma,=20 oligoastrocytoma WHO grade III; ependymoblastoma; glioblastoma, = medulloblastoma,=20 atypical teratoid rhabdoid tumor (ATRT) WHO grade IV] was = 2.00 =B1 0.46.=20 In comparison to 22 low grade tumors [pilocytic astrocytoma, = dysembryoplastic=20 neuroepthelial tumor (DNT), desmoplastic infantile ganglioglioma (DIG) = WHO grade=20 I; diffuse astrocytoma, pleomorphic xanthoastrocytoma WHO grade II], the = mean=20 MET-uptake was lower (1.84 =B1 0.31). However, a = differentiation between=20 low grade and high grade tumors was not possible (Student=92s = t-test;=20 P =3D 0.36). MET-uptake in the different histological = tumor types=20 and WHO grades is summarized in Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab6">6</A>.<A=20 name=3DTab6></A> <DIV class=3DCapt>Table 6 Maximum = MET-uptake=20 relative to corresponding control region within tumors of different = histological=20 types and non tumorous lesions </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"=B1"></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Histological diagnosis and WHO grade</TH> <TH align=3Dleft char=3D"."> n </TH> <TH align=3Dleft char=3D"."> n a </TH> <TH align=3Dleft char=3D"=B1"> Relative MET-uptake = (mean =B1 SDb)=20 </TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D4> Relative MET uptake in different = tumors</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pilocytic astrocytoma I</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"=B1"> 2.11 =B1 0.88</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma II</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"=B1"> 1.69 =B1 0.50</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pleomorphic xanthoastrocytoma II</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"=B1"> 2.23 =B1 0.48</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma III</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"=B1"> 2.61 =B1 0.73</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Oligoastrocytoma III</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 3</TD> <TD align=3Dchar char=3D"=B1"> 2.61 =B1 0.24</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Glioblastoma IV</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"=B1"> 1.70 =B1 0.55</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Medulloblastoma IV</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"=B1"> 1.78 =B1 0.55</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Atypical teratoid rhabdoid tumor IV</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"=B1"> 1.36 =B1 0.71</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoma II</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 0.97</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoblastoma IV</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 1.95</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> DNT I</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 2.04</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Desmoplastic infantile ganglioglioma I</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 2.01</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Non tumor lesions</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dchar char=3D"=B1"> 1.04 =B1 0.22</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Total</TD> <TD align=3Dchar char=3D"."> 39</TD> <TD align=3Dchar char=3D"."> 48</TD> <TD align=3Dleft char=3D"=B1"> </TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">A total of 48 PET investigations were performed in 39=20 patients</DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">aNumber of MET-PET investigations = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">bStandard deviation = </DIV></DIV></DIV></DIV></DIV> The MET-uptake differed significantly (Student=92s = t-test;=20 P =3D 0.02) when focused on the histologically more = homogeneous=20 subgroup of diffuse astrocytoma WHO grade II (1.69 =B1 0.50) = and=20 anaplastic astrocytoma WHO grade III (2.61 =B1 0.73). The MET-uptake in WHO grade I tumors, especially in = pilocytic=20 astrocytomas (2.11 =B1 0.88) was higher when compared to WHO = grade II=20 astrocytomas (1.69 =B1 0.50), but the difference did not reach = statistical significance (Student=92s t-test; = P =3D 0.28).=20 </DIV> <DIV class=3D""><A name=3DSec6></A> <HR> <DIV class=3Dheading2>Discussion</DIV> Our findings suggest that MET-PET has diagnostic relevance = in a=20 selected patient population including children and young adults and is = able to=20 distinguish brain tumors and non-tumorous brain lesions with a high = sensitivity=20 (83%) and specificity (92%). Therefore, MET-PET may be helpful = especially in=20 this group of patients when results of structural routine diagnostic = procedures=20 are not sufficient enough to obtain a treatment decision and its = planning. Due to the reduced MET-uptake in healthy brain tissue and, = therefore, a increased contrast between normal brain tissue and a = tumorous=20 lesion, MET-PET is superior to FDG-PET in tumor detection and assessment = of=20 tumor dimensions [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR9">9</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR22">22</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR23">23</A></CITE>].=20 Utriainen and co-workers described that 22 of 23 childhood brain tumors=20 exhibited higher MET accumulation in the tumor than in the adjacent = brain tissue=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>].=20 This observation supports our findings and may indicate that MET-PET is = not only=20 highly sensitive but also very specific. However, four low grade tumors (two patients with = pilocytic=20 astrocytoma and two patients with astrocytoma WHO grade II) were = classified=20 false negative. Low MET-uptake in a proportion of WHO grade II = astrocytomas is a=20 known feature of this histological entity in adult patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 In contrast, in our study pilocytic astrocytoma WHO grade I demonstrated = relatively high MET-uptake (2.11 =B1 0.88) when compared to = astrocytoma=20 WHO grade II (1.69 =B1 0.50). This has also been observed in a = previous=20 study [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 Histopathological features of pilocytic astrocytoma include mitosis,=20 microvascular proliferation and infiltration, but are not signs of = malignancy in=20 this tumor entity. In adult patients with gliomas, both mitotic activity = and=20 increased vascularization correlate with high MET-uptake, which may = explain the=20 high MET-uptake in pilocytic astrocytomas [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR5">5</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>].=20 In the two patients with false negative findings, low MET-uptake might = be=20 influenced by a decreased degree of microvascular proliferation in the = pilocytic=20 astrocytoma. Additionally, MET-uptake in one patient with suspected = recurrent=20 medulloblastoma was false negative in several small areas (uptake ratio = of 1.22)=20 and tumor progression occurred 5 months later. However, the uptake = pattern=20 of small lesions may be underestimated due to partial volume effects. = Modern=20 positron cameras like the ECAT EXACT HR have a transaxial resolution of=20 3.6 mm full width at half maximum, and, therefore small tumors = might be=20 hidden by normal brain uptake. Moderate MET-uptake was also observed in=20 embryonal tumors but all patients with medulloblastoma suffered from = recurrent=20 tumor at the time of examination. They had previously undergone = chemotherapy=20 and/or radiation therapy or they currently received chemotherapy which = might=20 have influenced the tracer uptake [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR7">7</A></CITE>].=20 In contrast to findings in adult patients, MET-uptake of = low grade=20 tumors did not differ significantly from high grade tumorous lesions = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 This observation is consistent with the findings of Utriainen and = colleagues=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>]=20 who found no association between MET-uptake and malignancy grade in = childhood=20 tumors. The failure to discriminate low grade from high grade tumors in = the=20 whole group probably is due to the confounding effect of high uptake in = the=20 pilocytic astrocytomas, which are more frequent in children than in = adults. Even=20 in adult patients, non-invasive grading is difficult when the = histological=20 subtype of the tumor is unknown because tumors of different histological = types=20 and grades show an overlapping pattern in MET-uptake [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 E.g., oligodendrogliomas WHO grade II might exhibit a MET-uptake = comparable to=20 those of anaplastic astrocytoma WHO grade III [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 If the histological subtype is known, non-invasive grading may be = possible in=20 children and young adults, as indicated by the significant difference of = MET-uptake between astrocytoma WHO grade II (1.69 =B1 0.50) = and=20 anaplastic astrocytoma WHO grade III (2.61 =B1 0.73). These = data suggest=20 that noninvasive diagnosis of malignant progression in gliomas, which is = of=20 crucial prognostic and therapeutic interest, may be possible with = MET-PET.=20 However, intraindividual changes of MET-uptake in the course of = malignant tumor=20 progression in this group of patients have not been investigated = systematically=20 so far. An important differential diagnosis of brain tumors with a = slightly=20 increased uptake pattern are inflammatory lesions. In our study a = patient with=20 ADEM showed a MET-uptake of 1.45 which is only slightly lower than the = threshold=20 of 1.48. This observation might be caused by a disruption of the blood = brain=20 barrier due to the inflammation. A small number of acute inflammatory = lesions=20 with mild MET-uptake have been observed in previous studies [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR24">24</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR25">25</A></CITE>].=20 <DIV class=3DPara> <DIV class=3D"">Sequential MET-PET monitoring of the course of the = disease may be=20 helpful in single cases. Figure <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig2">2</A>=20 shows the course of disease in a 10-year-old boy with a pleomorphic=20 xanthoastrocytoma WHO grade II. He was investigated three times using = MET-PET=20 within 3 years. The tumor was localized in the left temporal lobe = and the=20 patient suffered from mild verbal amnesia at the time of first diagnosis = (left=20 image). In the histopathological work-up, the tumor yielded areas of = increased=20 Ki67-MIB1 proliferation index up to 10. Therefore, close monitoring was=20 recommended. In follow-up scans, the tumor recurred early 5 months = after=20 initial surgery and 3 months after surgery of recurrent tumor, = respectively=20 (Fig. <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig2">2</A>).=20 This demonstrates that even repeated PET studies may be feasible in a = single=20 child revealing important insight into the disease state.=20 <DIV class=3DFigure><A name=3DFig2></A><IMG=20 alt=3DMediaObjects/11060_2009_9953_Fig2_HTML.jpg=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/MediaObjects/= 11060_2009_9953_Fig2_HTML.jpg"></DIV> <DIV class=3DCapt>Fig. 2 Course of = disease in=20 a 10-year-old boy with a pleomorphic xanthoastrocytoma WHO grade II. The = tumor=20 is localized in the left temporal lobe (left image). In follow-up = scans,=20 the tumor recurs early 5 months after initial surgery and 3 months after = surgery=20 of recurrent tumor, respectively </DIV> <HR> </DIV></DIV> In conclusion, MET-PET in children and young adults is = feasible and=20 should be performed after critical consideration of the indication for a = MET-PET=20 examination in this group of patients when additional information is = needed for=20 the differentiation from non-tumorous lesions before an invasive = procedure is=20 initiated. </DIV> <DIV class=3DAcknowledgments><SPAN=20 class=3DAcknowledgmentsHeading>Acknowledgment We=20 thank Mrs. U. Juchellek, E. Bannemer, R. Rusniak, C. Selbach and A. = Derici for=20 their gentle and compassionate care of the little patients and their=20 parents. <DIV class=3DFormalPara> <DIV class=3D"">Open=20 Access This article is distributed under the terms of = the=20 Creative Commons Attribution Noncommercial License which permits any=20 noncommercial use, distribution, and reproduction in any medium, = provided the=20 original author(s) and source are credited. </DIV></DIV></DIV> <HR> <H2><A name=3DBib1></A>References </H2> <TABLE> <TBODY class=3DCitation> <TR vAlign=3Dtop> <TD>1.</TD> <TD><A name=3DCR1></A>Jacobs AH, Dittmar C, Winkeler A, Garlip G, = Heiss WD=20 (2002) Molecular imaging of gliomas. 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From: Subject: 10.1007/s11060-009-9953-x Date: Tue, 28 Jul 2009 13:00:04 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CA0F83.531507A0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CA0F83.531507A0 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.springerlink.com/content/w74xq54758322wm2/fulltext.html 10.1007/s11060-009-9953-x</TIT= LE> <META http-equiv=3DContent-Type content=3D"text/html; = charset=3DISO-8859-1"><LINK=20 href=3D"http://www.springerlink.com/config/css/A++_common.css" = type=3Dtext/css=20 rel=3DstyleSheet><LINK=20 href=3D"http://www.springerlink.com/config/css/content_A++_SpringerLink.c= ss"=20 type=3Dtext/css rel=3DstyleSheet> <META content=3D"MSHTML 6.00.6000.16850" name=3DGENERATOR></HEAD> <BODY class=3Dfor-print> <TABLE cellPadding=3D2 border=3D1> <TBODY> <TR class=3Dheader> <TD>Journal of Neuro-Oncology</TD></TR> <TR> <TD>=A9 The Author(s) 2009</TD></TR> <TR> <TD>10.1007/s11060-009-9953-x</TD></TR></TBODY></TABLE> <H2 class=3Drubric>Clinical Study - Patient Study</H2> <DIV class=3DHeading1><A name=3Dtitle></A>[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-Methionine = positron=20 emission tomography in the management of children and young adults with = brain=20 tumors </DIV> Norbert Galldiks1 <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#ContactOfAuthor1"><IMG=20 alt=3D"Contact Information"=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/contact.gif" = border=3D0></A>, Lutz W. Kracht2,=20 Frank Berthold3, Hrvoje Miletic4,=20 Johannes C. Klein2, 7, Karl Herholz2, = 5,=20 Andreas H. Jacobs2, 6 and=20 Wolf-Dieter Heiss2 <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff1></A>(1) </TD> <TD>Department of Neurology, University of = Cologne, Kerpener Str. 62, 50924 Cologne,=20 Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff2></A>(2) </TD> <TD>Max Planck-Institute for Neurological=20 Research, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff3></A>(3) </TD> <TD>Department of Paediatric Oncology, = University=20 of Cologne, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff4></A>(4) </TD> <TD>Department of Neuropathology, = University of=20 Cologne, Cologne, Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff5></A>(5) </TD> <TD>Present address: Wolfson = Molecular=20 Imaging Centre, University of Manchester, Manchester,=20 UK</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff6></A>(6) </TD> <TD>Present address: Department of=20 Neurology, Klinikum Fulda, = Germany</TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><A = name=3DAff7></A>(7) </TD> <TD>Present address: Department of=20 Neurology, University of Frankfurt, Frankfurt,=20 Germany</TD></TR></TBODY></TABLE> <A name=3DContactOfAuthor1></A> <TABLE class=3DContact> <TBODY> <TR> <TD vAlign=3Dtop><IMG alt=3D"Contact Information"=20 = src=3D"http://www.springerlink.com/content/w74xq54758322wm2/contact.gif" = border=3D0></TD> = <TD>Norbert Galldiks</STRO= NG> Email:=20 <A=20 = href=3D"mailto:Norbert.Galldiks@uk-koeln.de">Norbert.Galldiks@uk-koeln.de= </A></TD></TR></TBODY></TABLE> Received:=20 4 March 2009 Accepted:=20 22 June 2009 Published online:=20 4 July 2009 <DIV class=3DAbstract><A name=3DAbs1></A><SPAN=20 class=3DAbstractHeading>Abstract Only a few=20 Methyl-[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-methionine = (MET)=20 positron emission tomography (PET) studies have focused on children and = young=20 adults with brain neoplasm. Due to radiation exposure, long scan = acquisition=20 time, and the need for sedation in young children MET-PET studies should = be=20 restricted to this group of patients when a decision for further therapy = is not=20 possible from routine diagnostic procedures alone, e.g., structural = imaging. We=20 investigated the diagnostic accuracy of MET-PET for the differentiation = between=20 tumorous and non-tumorous lesions in this group of patients. Forty eight = MET-PET=20 scans from 39 patients aged from 2 to 21 years (mean=20 15 =B1 5.0 years) were analyzed. The MET tumor-uptake = relative to a=20 corresponding control region was calculated. A receiver operating = characteristic=20 (ROC) was performed to determine the MET-uptake value that best = distinguishes=20 tumorous from non-tumorous brain lesions. A differentiation between = tumorous=20 (n =3D 39) and non-tumorous brain lesions=20 (n =3D 9) was possible at a threshold of 1.48 of = relative=20 MET-uptake with a sensitivity of 83% and a specificity of 92%, = respectively. A=20 differentiation between high grade malignant lesions (mean=20 MET-uptake =3D 2.00 =B1 0.46) and low grade tumors = (mean=20 MET-uptake =3D 1.84 =B1 0.31) was not possible. = There was a=20 significant difference in MET-uptake between the histologically = homogeneous=20 subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO = grade III=20 (P =3D 0.02). MET-PET might be a useful tool to = differentiate=20 tumorous from non-tumorous lesions in children and young adults when a = decision=20 for further therapy is difficult or impossible from routine structural = imaging=20 procedures alone. </DIV> Keywords Brain=20 tumor - Children - PET - Methionine -&= nbsp;Molecular=20 imaging <DIV class=3DArticleNote>Norbert Galldiks and Lutz W. = Kracht have=20 contributed equally to this work.</DIV> <DIV class=3D""><A name=3DSec1></A> <HR> <DIV class=3Dheading2>Introduction</DIV> Methyl-[11C]-<SPAN=20 style=3D"FONT-VARIANT: small-caps">l-methionine = (MET)=20 positron emission tomography (PET) is a well established method in the = diagnosis=20 and management of adult patients suffering from brain tumors. Besides = less=20 common tumors of the cranial cavity (e.g., embryogenic tumors, = glioneural=20 tumors, lymphomas, meningiomas) MET is incorporated into malignant = gliomas=20 (e.g., anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic=20 oligodendroglioma, glioblastoma multiforme), even in low grade gliomas = (e.g.,=20 WHO-grade II astrocytoma), and it is employed in the management of these = patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>].=20 MET is a sensitive tracer in tumor detection. In adults, it = differentiates=20 benign from malignant lesions with high sensitivity and specificity with = comparatively low background activity in normal brain tissue [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>].=20 MET-uptake correlates to cell proliferation in cell culture [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR3">3</A></CITE>],=20 Ki-67 expression [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR4">4</A></CITE>],=20 cell nuclear antigen expression [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR5">5</A></CITE>]=20 and microvessel density [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>],=20 indicating its role as a marker for active tumor proliferation and = angiogenesis.=20 In addition it seems to be useful in monitoring chemotherapy in patients = with=20 brain tumors [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR7">7</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR8">8</A></CITE>].=20 The main advantage of amino acid tracers when compared to=20 [18F]-2-fluoro-2-deoxy-<SPAN=20 style=3D"FONT-VARIANT: small-caps">d-glucose (FDG) = is the=20 excellent delineation of tumors extent [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR9">9</A></CITE>].=20 Despite this good imaging properties of MET-PET only a few = studies=20 have focused on children and young adults with brain neoplasms [<CITE><A = href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR10">10</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>].=20 Pirotte and co-workers provided evidence that MET- and FDG-PET improves = the=20 diagnostic yield in stereotactic brain biopsies and surgical management = of brain=20 tumors in children [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR11">11</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR13">13</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR14">14</A></CITE>].=20 In planning a PET scan for a child, various aspects need=20 consideration. For practical use and implementation of PET in children = see=20 Borgwardt et al. [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR15">15</A></CITE>].=20 Because molecular imaging can not replace structural imaging modalities = like=20 magnetic resonance imaging (MRI) or computed tomography (CT), it is = always a=20 supplementary investigation with radioactive exposure and comparatively = long=20 scan times. In respect of the effective radiation dose, whole-body = distribution=20 of FDG in children differed from adults: a greater proportion of the = injected=20 activity accumulated into the brain and less was excreted to urine = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR16">16</A></CITE>].=20 The dose of the injected radionuclide has to be adjusted for body = weight. In=20 addition, in children sedation or even general anesthesia especially in = very=20 young children is necessary to avoid patient movement. PET should be = restricted=20 to children with brain tumors where a clear decision for further therapy = planning is not possible from structural routine imaging alone. We investigated the diagnostic accuracy of MET-PET for the = differentiation between tumorous and non-tumorous lesions in this = selected group=20 of patients. </DIV> <DIV class=3D""><A name=3DSec2></A> <HR> <DIV class=3Dheading2>Patients and methods</DIV> <DIV class=3D""><A name=3DSec3></A> <DIV class=3DHeading3>Patients</DIV> Thirty-nine patients were included in the study. At the = time of=20 MET-PET investigation, the mean age of all patients was=20 15 =B1 5.0 years (range 2=9621 years). The patients = were=20 referred to the PET-unit of the Max-Planck-Institute for Neurological = Research=20 in Cologne, Germany because decision from MRI findings was difficult for = further=20 diagnostic procedures or therapy planning. A total of 48 MET-PET scans = were=20 performed for all patients. Two or more investigations were performed in = 6=20 patients during follow up. The purpose of the scan and potential risks = were=20 explained to the patients or their legal guardians before they gave = their=20 informed consent to the investigation. In order to differentiate between children and young = adults, the=20 threshold of age was set at 15 years. In the literature, a clear = definition=20 of a young adult was not available; therefore, the threshold of = 15 years=20 was set in the middle of the period of life between 10 and = 20 years, which=20 is the current definition of adolescence by the World Health = Organization (WHO).=20 In our collective, at the time of MET-PET imaging 17 patients were under = the age=20 of 15 years. To evaluate the diagnostic accuracy of MET-PET for the=20 differentiation between tumorous and non-tumorous lesions in this group = of=20 patients, routine diagnostic procedures like histological examinations = and=20 follow-up structural imaging (MRI or CT scans with contrast enhancing = agents)=20 were performed. Follow-up structural imaging was performed to confirm or = to=20 exclude a change of the lesion size over the course of the disease. = Structural=20 imaging procedures were performed within the clinical routine = periodically every=20 3=9612 months, depending on the WHO-grade of the brain tumor. E.g., = a=20 low-grade tumor was examined every 12 months, a WHO-grade IV tumor = was=20 examined every 3=966 months. Recurrence of a brain tumor was = defined=20 according to the Macdonald criteria (gadolinium enhancement or tumor = enlargement=20 ≥25%) [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR17">17</A></CITE>].=20 Furthermore, after clinical deterioration or occurrence of new symptoms, = structural imaging was performed promptly. After MET-PET imaging, the = mean=20 follow-up (imaging procedures like MRI or CT and/or clinically) was=20 25.5 =B1 43.3 months. Additionally, clinical aspects like = an=20 asymptomatic course of the disease, therapy response (e.g. = anticonvulsive=20 medication, corticosteroids) or a deterioration of symptoms were = considered as=20 well. <DIV class=3DPara> <DIV class=3D"">In all patients in which a tumorous lesion=20 (n =3D 31) was suspected (primary tumor or = recurrent/residual=20 tumor), the diagnosis was confirmed histologically during the course of = the=20 disease (Tables <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab1">1</A>,=20 <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab2">2</A>).=20 In patients with a non-tumorous lesion (n =3D 8), the = diagnosis=20 was confirmed histologically, clinically, by imaging results (MRI or CT = scan),=20 or clinically in combination with follow-up imaging results = (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab1></A> <DIV class=3DCapt>Table 1 Individual patient=20 data </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft> Newly diagnosed (ND)/recurrence (REC)</TH> <TH align=3Dleft> Sxa </TH> <TH align=3Dleft> Rxb </TH> <TH align=3Dleft> Cxc </TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right fronto- parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> 3rd ventricle</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Sellar region</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> DNT</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> DIG</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Right parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left precentral</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Quadrigeminal plate</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pleomorphic xanthoastrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 16</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Ependymoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 17</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 18</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 19</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left pericentral</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 20</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 21</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left temporo-parietal</TD> <TD align=3Dleft> ND/RECd </TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 22</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right internal capsula</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 23</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 24</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 25</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 26</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 27</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Pons</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 28</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right cerebellum</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 29</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Ependymoblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right fronto-temporal</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 30</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Brainstem</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> Yes</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 31</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right temporo-occipital</TD> <TD align=3Dleft> REC</TD> <TD align=3Dleft> Yes</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 32</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 33</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 34</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Epilepsy</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 35</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pineal cyst</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Pineal gland</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 36</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ADEM</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 37</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left parieto-occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 38</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 39</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Stroke PCA</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dleft> ND</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD> <TD align=3Dleft> No</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Individual data of 39 children and young adults with = suspected=20 newly diagnosed or recurrent brain tumor who underwent = MET-PET</DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">DIG Desmoplastic infantile ganglioglioma, = DNT=20 dysembryoplastic neuroepithelial tumor, ATRT atypical teratoid = rhabdoid=20 tumor, ADEM acute demyelinating encephalomyelitis, PCA = posterior=20 cerebral artery </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">aSurgery before MET-PET </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">bRadiation therapy before MET-PET = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">cChemotherapy before MET-PET </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">dPatients were investigated at the time of = first=20 diagnosis and at the time of suspected recurrence </DIV></DIV></DIV><A=20 name=3DTab2></A> <DIV class=3DCapt>Table 2 Number = of patients=20 with tumors of different histological types and non-tumorous lesions = </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Histological diagnosis and WHO grade</TH> <TH align=3Dleft> Total</TH> <TH align=3Dleft> Under age of 15</TH> <TH align=3Dleft> 15=9621 years</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D4> Histological diagnoses</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pilocytic astrocytoma I</TD> <TD align=3Dleft> 6</TD> <TD align=3Dleft> 3</TD> <TD align=3Dleft> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma II</TD> <TD align=3Dleft> 6</TD> <TD align=3Dleft> 3</TD> <TD align=3Dleft> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pleomorphic xanthoastrocytoma II</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma III</TD> <TD align=3Dleft> 4</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Oligoastrocytoma III</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Glioblastoma IV</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Medulloblastoma IV</TD> <TD align=3Dleft> 4</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Atypical teratoid rhabdoid tumor IV</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 2</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoma II</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoblastoma IV</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> DNT I</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Desmoplastic infantile ganglioglioma I</TD> <TD align=3Dleft> 1</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Non-tumor lesions</TD> <TD align=3Dleft> 8</TD> <TD align=3Dleft> 0</TD> <TD align=3Dleft> 8</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Total</TD> <TD align=3Dleft> 39</TD> <TD align=3Dleft> 17</TD> <TD align=3Dleft> 22</TD></TR></TBODY></TABLE></DIV></DIV> <DIV class=3DPara> <DIV class=3D"">In 16 MET-PET scans of 15 patients (5 patients under the = age of=20 15 years) a primary brain tumor was suspected on MRI (Table <A = href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab3">3</A>).=20 In these patients MET-PET was performed to confirm MRI findings and to = give=20 additional information about extent and dignity of the lesion.<A = name=3DTab3></A> <DIV class=3DCapt>Table 3 Patients = with a=20 suspected primary brain tumor on MRI </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> DNT</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> DIG</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Right parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Quadrigeminal plate</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 32</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 33</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Cortical malformation</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 34</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Epilepsy</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right fronto-parietal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 35</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pineal cyst</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Pineal gland</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 36</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ADEM</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Right occipital</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 37</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left parieto-occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 38</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Multiple sclerosis</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 39</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Stroke PCA</TD> <TD align=3Dleft> /</TD> <TD align=3Dleft> Left occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">In these patients PET was performed to confirm MRI = findings and to=20 give additional information about extent and dignity of the lesion = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) or by = follow-up MRI or CT scans </DIV></DIV></DIV></DIV></DIV> Presence or absence of a primary tumor at the time of = MET-PET=20 imaging (n =3D 16 in 15 patients) was confirmed (i)=20 histologically after the MET-PET examination by surgery or stereotactic = biopsy=20 (n =3D 8), (ii) clinically (n =3D 4), = (iii) or by=20 follow-up MRI or CT scans (n =3D 3). <DIV class=3DPara> <DIV class=3D"">In 21 MET-PET scans of 20 patients (11 patients under = the age of=20 15 years) a recurrent or residual tumor was suspected after = therapy, but a=20 clear differentiation from posttherapeutic changes was not possible from = MRI=20 alone (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab4">4</A>).<A=20 name=3DTab4></A> <DIV class=3DCapt>Table 4 Patients = with=20 suspected recurrent tumor after therapy in which a clear differentiation = from=20 posttherapeutic changes was not possible from MRI alone </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> 3rd ventricle</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 3</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Left thalamus</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Sellar region</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pilocytic astrocytoma</TD> <TD align=3Dleft> I</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 5</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left frontal</TD> <TD align=3Dleft char=3D"."> </TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 6</TD> <TD align=3Dchar char=3D"."> 16</TD> <TD align=3Dchar char=3D"."> 13</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Ependymoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 7</TD> <TD align=3Dchar char=3D"."> 17</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 8</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right basal ganglia</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 9</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left pericentral</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 10</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dchar char=3D"."> 14</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 11</TD> <TD align=3Dchar char=3D"."> 22</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Right internal capsula</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 12</TD> <TD align=3Dchar char=3D"."> 23</TD> <TD align=3Dchar char=3D"."> 18</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 13</TD> <TD align=3Dchar char=3D"."> 24</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Glioblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right thalamus</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 14</TD> <TD align=3Dchar char=3D"."> 25</TD> <TD align=3Dchar char=3D"."> 20</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Left cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 15</TD> <TD align=3Dchar char=3D"."> 26</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right frontal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 16</TD> <TD align=3Dchar char=3D"."> 27</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Pons</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 17</TD> <TD align=3Dchar char=3D"."> 28</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Medulloblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right cerebellum</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 18</TD> <TD align=3Dchar char=3D"."> 29</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Ependymoblastoma</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right fronto-temporal</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 3</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 19</TD> <TD align=3Dchar char=3D"."> 30</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Brainstem</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 2</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 20</TD> <TD align=3Dchar char=3D"."> 31</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> ATRT</TD> <TD align=3Dleft> IV</TD> <TD align=3Dleft> Right temporo-occipital</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 4</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) by = follow-up=20 MRI or CT scans, (4) or clinically in combination with follow-up imaging = results=20 </DIV></DIV></DIV></DIV></DIV> Presence or absence of a recurrent or residual tumor with = previously=20 histologically confirmed diagnosis at the time of MET-PET imaging=20 (n =3D 21 in 20 patients) was confirmed (i) by further=20 histological diagnosis after surgery or stereotactic biopsy=20 (n =3D 5), (ii) clinically (n =3D 2), = (iii) by=20 follow-up MRI or CT scans (n =3D 5), (iv) or clinically = in=20 combination with follow-up imaging results (n =3D 8). = <DIV class=3DPara> <DIV class=3D"">Additionally, 4 patients were examined initially when a = primary=20 brain tumor was suspected on MRI and, afterward, when a recurrent or = residual=20 tumor was suspected after therapy (Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab5">5</A>).=20 In these 4 patients, 11 MET-PET scans were performed (one patient of = these 4=20 patients was under the age of 15 years).<A name=3DTab5></A> <DIV class=3DCapt>Table 5 Patients = with brain=20 tumor which were examined initially when a primary brain tumor was = suspected on=20 MRI and, afterward, when a recurrent or residual tumor was suspected = after=20 therapy </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> #</TH> <TH align=3Dleft char=3D"."> Pat. no.</TH> <TH align=3Dleft char=3D"."> Age [years]</TH> <TH align=3Dleft> Gender (F =3D female = M =3D male)</TH> <TH align=3Dleft> Diagnosis</TH> <TH align=3Dleft> WHO grade</TH> <TH align=3Dleft> Localization</TH> <TH align=3Dleft char=3D"."> Number of MET-PET scans [n] </TH> <TH align=3Dleft char=3D"."> Diagnosis confirmed by</TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> 1</TD> <TD align=3Dchar char=3D"."> 11</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 2</TD> <TD align=3Dchar char=3D"."> 12</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Astrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left precentral</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 3</TD> <TD align=3Dchar char=3D"."> 15</TD> <TD align=3Dchar char=3D"."> 10</TD> <TD align=3Dleft> M</TD> <TD align=3Dleft> Pleomorphic xanthoastrocytoma</TD> <TD align=3Dleft> II</TD> <TD align=3Dleft> Left temporal</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"."> 1,1</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> 4</TD> <TD align=3Dchar char=3D"."> 21</TD> <TD align=3Dchar char=3D"."> 19</TD> <TD align=3Dleft> F</TD> <TD align=3Dleft> Oligoastrocytoma</TD> <TD align=3Dleft> III</TD> <TD align=3Dleft> Left temporo-parietal</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 4,1</TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">Diagnosis was confirmed (1) histologically after the = MET-PET=20 examination by surgery or stereotactic biopsy, (2) clinically, (3) by = follow-up=20 MRI or CT scans, (4) or clinically in combination with follow-up imaging = results=20 </DIV></DIV></DIV></DIV></DIV> Presence of primary tumor and recurrent or residual tumor, = respectively, was confirmed (i) both histologically = (n =3D 1),=20 (ii) clinically and histologically (n =3D 1), (iii) or = clinically=20 in combination with imaging results and histologically = (n =3D 2).=20 Most tumors were located in critical areas like basal = ganglia,=20 midbrain, and brainstem or next to motor areas in the pericentral region = or=20 speech relevant areas in the left temporal lobe. </DIV> <DIV class=3D""><A name=3DSec4></A> <DIV class=3DHeading3>Methods</DIV> Altogether, 48 MET-PET studies of the 39 patients were = performed=20 either on an ECAT EXACT HR or ECAT EXACT scanner (Siemens-CTI, = Knoxville, TN)=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR19">19</A></CITE>].=20 In one child a mild sedation and in four children a general anesthesia = was=20 necessary to avoid patient movement. In these cases, the children were = under the=20 age of 12 years. 11 MBq/kg bodyweight MET (maximum = 740 MBq) were=20 injected intravenously. MET was synthesized according to the method of = Berger et=20 al. [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR20">20</A></CITE>].=20 Tracer accumulation was recorded over 60 min directly after tracer=20 injection or over 40 min beginning 20 min after tracer = injection. The=20 entire brain was scanned in 47 transaxial slices. Summed activity from = 20 to=20 60 min after tracer injection was used for image reconstruction. = Scans were=20 corrected for attenuation and scatter. Spatial resolution was 6 mm = or=20 better in all dimensions. As described previously, a circular region of interest = (ROI) of=20 7 mm diameter was placed in the area of maximum MET-uptake = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 Mean uptake of this ROI was determined relative to a control region in = the=20 unaffected hemisphere which was obtained by mirroring the ROI along the = medial=20 sagittal plane. In midline or brainstem lesions the reference ROI was = placed in=20 the fronto-lateral cortex of the unaffected hemisphere. To determine the relative MET-uptake value that best = distinguishes=20 tumorous from non-tumorous brain lesions, a receiver operating = characteristic=20 (ROC) analysis was performed by varying the threshold of MET-uptake over = the=20 whole range of values and calculating sensitivity and specificity for = each=20 value. For statistical analyses, SPSS version 10.0.7 (SPSS Inc., = Chicago,=20 Illinois) was used. Graphs were plotted with SigmaPlot, version 7.0 = (SPSS Inc.,=20 Chicago, Illinois). </DIV></DIV> <DIV class=3D""><A name=3DSec5></A> <HR> <DIV class=3Dheading2>Results</DIV> <DIV class=3DPara> <DIV class=3D"">At a threshold of 1.48, relative MET-uptake = differentiation=20 between tumorous (n =3D 39) and non-tumorous brain = lesions=20 (n =3D 9) was possible with a sensitivity of 83% and = specificity=20 of 92% (area under the curve =3D 0.94, 95%-confidence=20 interval =3D 0.87=961.00; Fig. <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig1">1</A>).=20 At this threshold, 8 of 9 non-tumorous lesions were classified correctly = by=20 using MET-PET imaging. The false-positive case was one patient with a = newly=20 developed contrast enhancing lesion in the pons 14 years after = treatment of=20 a medulloblastoma with a MET-uptake of 1.53. This lesion disappeared = slowly=20 without treatment in follow-up MRI examinations 1 and 4 months = after the=20 PET investigation. At a threshold greater than 1.53, the specificity was = 100%=20 without false positive findings.=20 <DIV class=3DFigure><A name=3DFig1></A><IMG=20 alt=3DMediaObjects/11060_2009_9953_Fig1_HTML.gif=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/MediaObjects/= 11060_2009_9953_Fig1_HTML.gif"></DIV> <DIV class=3DCapt>Fig. 1 ROC = analysis of=20 relative [11C-MET]-uptake to differentiate tumor from = non-tumorous=20 lesions </DIV> <HR> </DIV></DIV> Thirty-four of 39 confirmed tumors were correctly = classified=20 positive. False negative findings included two pilocytic astrocytoma WHO = grade I=20 and two diffuse astrocytoma WHO grade II. In one child with a suspected=20 medulloblastoma, several small areas with a slight MET-uptake of 1.22 = were=20 observed. However, this uptake had to be classified as false negative, = because a=20 manifest tumor progression could be diagnosed 5 months later. At a threshold of 1.48, relative MET-uptake = differentiation between=20 tumorous and non-tumorous brain lesions was possible in the group of = patients=20 under the age of 15 years (n =3D 17) with a = sensitivity of=20 91% and a specificity of 100%. <DIV class=3DPara> <DIV class=3D"">The mean MET-uptake in 17 high grade tumors = [astrocytoma,=20 oligoastrocytoma WHO grade III; ependymoblastoma; glioblastoma, = medulloblastoma,=20 atypical teratoid rhabdoid tumor (ATRT) WHO grade IV] was = 2.00 =B1 0.46.=20 In comparison to 22 low grade tumors [pilocytic astrocytoma, = dysembryoplastic=20 neuroepthelial tumor (DNT), desmoplastic infantile ganglioglioma (DIG) = WHO grade=20 I; diffuse astrocytoma, pleomorphic xanthoastrocytoma WHO grade II], the = mean=20 MET-uptake was lower (1.84 =B1 0.31). However, a = differentiation between=20 low grade and high grade tumors was not possible (Student=92s = t-test;=20 P =3D 0.36). MET-uptake in the different histological = tumor types=20 and WHO grades is summarized in Table <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Tab6">6</A>.<A=20 name=3DTab6></A> <DIV class=3DCapt>Table 6 Maximum = MET-uptake=20 relative to corresponding control region within tumors of different = histological=20 types and non tumorous lesions </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"."> <COL align=3Dchar char=3D"=B1"></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> Histological diagnosis and WHO grade</TH> <TH align=3Dleft char=3D"."> n </TH> <TH align=3Dleft char=3D"."> n a </TH> <TH align=3Dleft char=3D"=B1"> Relative MET-uptake = (mean =B1 SDb)=20 </TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D4> Relative MET uptake in different = tumors</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pilocytic astrocytoma I</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"=B1"> 2.11 =B1 0.88</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma II</TD> <TD align=3Dchar char=3D"."> 6</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"=B1"> 1.69 =B1 0.50</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Pleomorphic xanthoastrocytoma II</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"=B1"> 2.23 =B1 0.48</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Astrocytoma III</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 5</TD> <TD align=3Dchar char=3D"=B1"> 2.61 =B1 0.73</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Oligoastrocytoma III</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 3</TD> <TD align=3Dchar char=3D"=B1"> 2.61 =B1 0.24</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Glioblastoma IV</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"=B1"> 1.70 =B1 0.55</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Medulloblastoma IV</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"."> 4</TD> <TD align=3Dchar char=3D"=B1"> 1.78 =B1 0.55</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Atypical teratoid rhabdoid tumor IV</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"."> 2</TD> <TD align=3Dchar char=3D"=B1"> 1.36 =B1 0.71</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoma II</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 0.97</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Ependymoblastoma IV</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 1.95</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> DNT I</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 2.04</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Desmoplastic infantile ganglioglioma I</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"."> 1</TD> <TD align=3Dchar char=3D"=B1"> 2.01</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Non tumor lesions</TD> <TD align=3Dchar char=3D"."> 8</TD> <TD align=3Dchar char=3D"."> 9</TD> <TD align=3Dchar char=3D"=B1"> 1.04 =B1 0.22</TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> Total</TD> <TD align=3Dchar char=3D"."> 39</TD> <TD align=3Dchar char=3D"."> 48</TD> <TD align=3Dleft char=3D"=B1"> </TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D"">A total of 48 PET investigations were performed in 39=20 patients</DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">aNumber of MET-PET investigations = </DIV></DIV> <DIV class=3DCaptCont> <DIV class=3D"">bStandard deviation = </DIV></DIV></DIV></DIV></DIV> The MET-uptake differed significantly (Student=92s = t-test;=20 P =3D 0.02) when focused on the histologically more = homogeneous=20 subgroup of diffuse astrocytoma WHO grade II (1.69 =B1 0.50) = and=20 anaplastic astrocytoma WHO grade III (2.61 =B1 0.73). The MET-uptake in WHO grade I tumors, especially in = pilocytic=20 astrocytomas (2.11 =B1 0.88) was higher when compared to WHO = grade II=20 astrocytomas (1.69 =B1 0.50), but the difference did not reach = statistical significance (Student=92s t-test; = P =3D 0.28).=20 </DIV> <DIV class=3D""><A name=3DSec6></A> <HR> <DIV class=3Dheading2>Discussion</DIV> Our findings suggest that MET-PET has diagnostic relevance = in a=20 selected patient population including children and young adults and is = able to=20 distinguish brain tumors and non-tumorous brain lesions with a high = sensitivity=20 (83%) and specificity (92%). Therefore, MET-PET may be helpful = especially in=20 this group of patients when results of structural routine diagnostic = procedures=20 are not sufficient enough to obtain a treatment decision and its = planning. Due to the reduced MET-uptake in healthy brain tissue and, = therefore, a increased contrast between normal brain tissue and a = tumorous=20 lesion, MET-PET is superior to FDG-PET in tumor detection and assessment = of=20 tumor dimensions [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR9">9</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR22">22</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR23">23</A></CITE>].=20 Utriainen and co-workers described that 22 of 23 childhood brain tumors=20 exhibited higher MET accumulation in the tumor than in the adjacent = brain tissue=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>].=20 This observation supports our findings and may indicate that MET-PET is = not only=20 highly sensitive but also very specific. However, four low grade tumors (two patients with = pilocytic=20 astrocytoma and two patients with astrocytoma WHO grade II) were = classified=20 false negative. Low MET-uptake in a proportion of WHO grade II = astrocytomas is a=20 known feature of this histological entity in adult patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 In contrast, in our study pilocytic astrocytoma WHO grade I demonstrated = relatively high MET-uptake (2.11 =B1 0.88) when compared to = astrocytoma=20 WHO grade II (1.69 =B1 0.50). This has also been observed in a = previous=20 study [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 Histopathological features of pilocytic astrocytoma include mitosis,=20 microvascular proliferation and infiltration, but are not signs of = malignancy in=20 this tumor entity. In adult patients with gliomas, both mitotic activity = and=20 increased vascularization correlate with high MET-uptake, which may = explain the=20 high MET-uptake in pilocytic astrocytomas [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR5">5</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>].=20 In the two patients with false negative findings, low MET-uptake might = be=20 influenced by a decreased degree of microvascular proliferation in the = pilocytic=20 astrocytoma. Additionally, MET-uptake in one patient with suspected = recurrent=20 medulloblastoma was false negative in several small areas (uptake ratio = of 1.22)=20 and tumor progression occurred 5 months later. However, the uptake = pattern=20 of small lesions may be underestimated due to partial volume effects. = Modern=20 positron cameras like the ECAT EXACT HR have a transaxial resolution of=20 3.6 mm full width at half maximum, and, therefore small tumors = might be=20 hidden by normal brain uptake. Moderate MET-uptake was also observed in=20 embryonal tumors but all patients with medulloblastoma suffered from = recurrent=20 tumor at the time of examination. They had previously undergone = chemotherapy=20 and/or radiation therapy or they currently received chemotherapy which = might=20 have influenced the tracer uptake [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR7">7</A></CITE>].=20 In contrast to findings in adult patients, MET-uptake of = low grade=20 tumors did not differ significantly from high grade tumorous lesions = [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR2">2</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 This observation is consistent with the findings of Utriainen and = colleagues=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR12">12</A></CITE>]=20 who found no association between MET-uptake and malignancy grade in = childhood=20 tumors. The failure to discriminate low grade from high grade tumors in = the=20 whole group probably is due to the confounding effect of high uptake in = the=20 pilocytic astrocytomas, which are more frequent in children than in = adults. Even=20 in adult patients, non-invasive grading is difficult when the = histological=20 subtype of the tumor is unknown because tumors of different histological = types=20 and grades show an overlapping pattern in MET-uptake [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 E.g., oligodendrogliomas WHO grade II might exhibit a MET-uptake = comparable to=20 those of anaplastic astrocytoma WHO grade III [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>].=20 If the histological subtype is known, non-invasive grading may be = possible in=20 children and young adults, as indicated by the significant difference of = MET-uptake between astrocytoma WHO grade II (1.69 =B1 0.50) = and=20 anaplastic astrocytoma WHO grade III (2.61 =B1 0.73). These = data suggest=20 that noninvasive diagnosis of malignant progression in gliomas, which is = of=20 crucial prognostic and therapeutic interest, may be possible with = MET-PET.=20 However, intraindividual changes of MET-uptake in the course of = malignant tumor=20 progression in this group of patients have not been investigated = systematically=20 so far. An important differential diagnosis of brain tumors with a = slightly=20 increased uptake pattern are inflammatory lesions. In our study a = patient with=20 ADEM showed a MET-uptake of 1.45 which is only slightly lower than the = threshold=20 of 1.48. This observation might be caused by a disruption of the blood = brain=20 barrier due to the inflammation. A small number of acute inflammatory = lesions=20 with mild MET-uptake have been observed in previous studies [<CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR21">21</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR24">24</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#CR25">25</A></CITE>].=20 <DIV class=3DPara> <DIV class=3D"">Sequential MET-PET monitoring of the course of the = disease may be=20 helpful in single cases. Figure <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig2">2</A>=20 shows the course of disease in a 10-year-old boy with a pleomorphic=20 xanthoastrocytoma WHO grade II. He was investigated three times using = MET-PET=20 within 3 years. The tumor was localized in the left temporal lobe = and the=20 patient suffered from mild verbal amnesia at the time of first diagnosis = (left=20 image). In the histopathological work-up, the tumor yielded areas of = increased=20 Ki67-MIB1 proliferation index up to 10. Therefore, close monitoring was=20 recommended. In follow-up scans, the tumor recurred early 5 months = after=20 initial surgery and 3 months after surgery of recurrent tumor, = respectively=20 (Fig. <A=20 href=3D"http://www.springerlink.com/content/w74xq54758322wm2/fulltext.htm= l#Fig2">2</A>).=20 This demonstrates that even repeated PET studies may be feasible in a = single=20 child revealing important insight into the disease state.=20 <DIV class=3DFigure><A name=3DFig2></A><IMG=20 alt=3DMediaObjects/11060_2009_9953_Fig2_HTML.jpg=20 src=3D"http://www.springerlink.com/content/w74xq54758322wm2/MediaObjects/= 11060_2009_9953_Fig2_HTML.jpg"></DIV> <DIV class=3DCapt>Fig. 2 Course of = disease in=20 a 10-year-old boy with a pleomorphic xanthoastrocytoma WHO grade II. The = tumor=20 is localized in the left temporal lobe (left image). In follow-up = scans,=20 the tumor recurs early 5 months after initial surgery and 3 months after = surgery=20 of recurrent tumor, respectively </DIV> <HR> </DIV></DIV> In conclusion, MET-PET in children and young adults is = feasible and=20 should be performed after critical consideration of the indication for a = MET-PET=20 examination in this group of patients when additional information is = needed for=20 the differentiation from non-tumorous lesions before an invasive = procedure is=20 initiated. </DIV> <DIV class=3DAcknowledgments><SPAN=20 class=3DAcknowledgmentsHeading>Acknowledgment We=20 thank Mrs. U. Juchellek, E. Bannemer, R. Rusniak, C. Selbach and A. = Derici for=20 their gentle and compassionate care of the little patients and their=20 parents. <DIV class=3DFormalPara> <DIV class=3D"">Open=20 Access This article is distributed under the terms of = the=20 Creative Commons Attribution Noncommercial License which permits any=20 noncommercial use, distribution, and reproduction in any medium, = provided the=20 original author(s) and source are credited. </DIV></DIV></DIV> <HR> <H2><A name=3DBib1></A>References </H2> <TABLE> <TBODY class=3DCitation> <TR vAlign=3Dtop> <TD>1.</TD> <TD><A name=3DCR1></A>Jacobs AH, Dittmar C, Winkeler A, Garlip G, = Heiss WD=20 (2002) Molecular imaging of gliomas. 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