| 1: AJNR Am J Neuroradiol. 2004 Jun-Jul;25(6):1121-3. |
|
-
Direct percutaneous intratumoral bleomycin injection for
palliative treatment of impending quadriplegia.
Duncan IC, Fourie PA, Alberts AS.
Unitas Interventional Unit, Unitas Hospital, Centurion, South Africa.
We describe a case of midcervical angiosarcoma causing compression of the
cervical spinal cord, producing rapidly progressive neurologic deficits. The
tumor had recurred despite previous resection and was refractory to
radiation and chemotherapy. Shrinkage of the tumor by percutaneous
embolization was not considered feasible. A single direct percutaneous
intratumoral injection of 15 U of bleomycin produced sufficient tumor
shrinkage to relieve the pressure on the spinal cord and thereby reverse
some of the neurologic deficits and give adequate palliation against
recurrence of this problem for the remainder of the patient's life. Direct
percutaneous intratumoral injection of bleomycin may thus be considered for
palliation when other treatment methods have failed to elicit a suitable
clinical response.
Publication Types:
PMID: 15205162 [PubMed - indexed for MEDLINE]
-
| 2: AJNR Am J Neuroradiol. 2004 Jun-Jul;25(6):1037-40. |
|
-
Appearance of an interhemispheric cyst associated with
agenesis of the corpus callosum.
Smith AS, Levine D.
Harvard Medical School and the Harvard-MIT Division of Health Science and
Technology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue,
Boston, MA 02215, USA.
We describe a fetus with agenesis of the corpus callosum (ACC) and
Dandy-Walker malformation that developed a frontal paramidline cyst late in
gestation. The interval appearance of the cyst occurred in concert with
increasing size of the lateral ventricles, which supports the hypothesis
that cysts associated with ACC can develop with increasing intraventricular
pressure. Recognition of the potential for a changing appearance of
neurologic abnormalities is important to providing appropriate patient
counseling.
Publication Types:
PMID: 15205144 [PubMed - indexed for MEDLINE]
-
| 3: AJNR Am J Neuroradiol. 2004 Jun-Jul;25(6):1028-33. |
|
-
MR imaging in the diagnosis of desmoplastic infantile
tumor: retrospective study of six cases.
Trehan G, Bruge H, Vinchon M, Khalil C, Ruchoux MM, Dhellemmes P, Ares
GS.
Department of Neuroradiology, Hopital Roger Salengro, Centre Hospitalier
Regional Universitaire de Lille, Lille, France.
BACKGROUND AND PURPOSE: Desmoplastic infantile tumors (DITs) are rare
supratentorial tumors of infancy with a favorable prognosis. Radiologic and
histologic features of DIT are misleading, and DIT may be misinterpreted as
a malignant lesion. We have studied the usefulness of MR imaging in the
diagnosis of these tumors. METHODS: Between 1995 and 2002, six DITs were
diagnosed in young children at our institution. Neuroimaging, age at
diagnosis, sex, clinical presentation, symptoms duration, follow-up, and
development were studied retrospectively. Contrast-enhanced CT and MR images
were available. MR study included T1-, T2-, and postgadolinium T1-weighted
sequences in the axial, sagittal, and coronal planes. RESULTS: These tumors
were massive and predominantly cystic, with preferential frontal and
parietal involvement. Typically, a DIT appears as a hypointense cystic mass
with an isointense peripheral solid component on T1-weighted MR images. The
peripheral solid component enhances after gadolinium administration. On
T2-weighted MR images, the cystic component is hyperintense and the solid
portion isointense or heterogeneous. The cystic portion is usually located
deep inside the lesion, whereas its solid portion is peripheral. Meningeal
enhancement and thickening adjacent to the solid portion of the tumor,
calcifications, bone abnormalities adjacent to the tumor consisting of
thinning and deformation were noted in 50% of our cases. Edema was usually
absent or moderate. Median follow-up was 32 months, and no recurrence was
noted except for one atypical case with incomplete excision, which led to
the patient's death. CONCLUSION: Despite their malignant appearance, MR
imaging features of DIT may help in the diagnosis and obviate unnecessary
chemotherapy or radiation therapy.
PMID: 15205142 [PubMed - indexed for MEDLINE]
-
| 4: AJNR Am J Neuroradiol. 2004 Jun-Jul;25(6):997-1005. |
|
-
Dynamic susceptibility contrast-enhanced perfusion and
conventional MR imaging findings for adult patients with cerebral primitive
neuroectodermal tumors.
Law M, Kazmi K, Wetzel S, Wang E, Iacob C, Zagzag D, Golfinos JG, Johnson
G.
Department of Radiology, New York University Medical Center, New York, NY
10016, USA.
BACKGROUND AND PURPOSE: Preoperative differentiation of primitive
neuroectodermal tumors (PNETs) from other tumors is important for
presurgical staging, intraoperative management, and postoperative treatment.
Dynamic, susceptibility-weighted, contrast-enhanced MR imaging can provide
in vivo assessment of the microvasculature in intracranial mass lesions. The
purpose of this study was to determine the perfusion characteristics of
adult cerebral PNETs and to compare those values with low and high grade
gliomas. METHODS: Conventional MR images of 12 adult patients with
pathologically proved cerebral PNETs were analyzed and provided a
preoperative diagnosis. Relative cerebral blood volume (rCBV) measurements
and estimates of the vascular permeability transfer constant, K(trans),
derived by a pharmacokinetic modeling algorithm, were also obtained. These
results were compared with rCBV and K(trans) values obtained in a group of
low grade gliomas (n = 30) and a group of high grade gliomas (n = 55) by
using a Student t test. RESULTS: On conventional MR images, PNETs were
generally well-defined contrast-enhancing masses with solid and cystic
components, little or no surrounding edema, and occasional regions of
susceptibility. The rCBV of cerebral PNETs was 4.76 +/- 1.99 SD, and the
K(trans) was 0.0033 +/- 0.0035. A comparative group of patients with low
grade gliomas (n = 30) had significantly lower rCBV (P <.0005) and lower
K(trans) (P <.05). Comparison with a group of high grade gliomas showed
no statistical significance in the rCBV and K(trans) (P =.53 and.19,
respectively). CONCLUSION: Dynamic, susceptibility-weighted,
contrast-enhanced MR imaging shows areas of increased cerebral blood volume
and vascular permeability in PNETs. These results may be helpful in the
diagnosis and preoperative differentiation between PNETs and other
intracranial mass lesions (such as low grade gliomas), which have decreased
perfusion but may sometimes have a similar conventional MR imaging
appearance.
PMID: 15205137 [PubMed - indexed for MEDLINE]
-
| 5: Arch Neurol. 2004 Sep;61(9):1451-3. |
|
-
Isolated relative afferent pupillary defect secondary to
contralateral midbrain compression.
Chen CJ, Scheufele M, Sheth M, Torabi A, Hogan N, Frohman EM.
Departments of Neurology and Ophthalmology, University of Texas Southwestern
Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
BACKGROUND: Relative afferent pupillary defects are typically related to
ipsilateral lesions within the anterior visual pathways. OBJECTIVE: To
describe a patient who had a workup for headache and was found to have an
isolated left relative afferent pupillary defect without any other
neurological findings. DESIGN: We review the neuroanatomy of the pupillary
light reflex pathway and emphasize the nasotemporal bias of decussating
fiber projections, which accounts for the relative afferent pupillary defect
contralateral to the described lesion.Result Magnetic resonance imaging of
the brain revealed a pineal tumor compressing the right rostral midbrain.
CONCLUSION: While rare, a relative afferent pupillary defect can
occasionally occur secondary to lesions in the postchiasmal pathways. In
these circumstances, the pupillary defect will be observed to be
contralateral to the side of the lesion.
Publication Types:
PMID: 15364693 [PubMed - indexed for MEDLINE]
-
| 6: Arch Neurol. 2004 Sep;61(9):1423-9. |
|
-
Multiple myeloma invasion of the central nervous system.
Schluterman KO, Fassas AB, Van Hemert RL, Harik SI.
Department of Neurology, University of Arkansas for Medical Sciences, 4301
W. Markham Street, Little Rock, AR 72205, USA. schlutermankeitho@uams.edu
BACKGROUND: Although neurologic manifestations often complicate the course
of patients with multiple myeloma (MM), direct central nervous system
invasion is rare. OBJECTIVE: To describe the neurologic symptoms and signs,
imaging, cerebrospinal fluid findings, and the clinical course of patients
with central nervous system myeloma invasion, all of whom had leptomeningeal
myelomatosis.Design and PARTICIPANTS: Review of 23 patients with MM and
leptomeningeal myelomatosis proven by malignant plasma cells in their
cerebrospinal fluid. SETTING: Tertiary-care university medical center.
RESULTS: Twenty-one patients had advanced-stage MM. Leptomeningeal
myelomatosis was diagnosed up to 29 months (median, 13 months) after
diagnosis of MM. Symptoms precipitating neurologic evaluation included
manifestations of diffuse cerebral dysfunction, cranial nerve palsies, and
spinal radiculopathies. Cerebrospinal fluid was abnormal in all patients,
usually exhibiting pleocytosis and elevated protein content, plus positive
cytologic findings. Specific magnetic resonance imaging findings suggestive
of central nervous system invasion were found in 70% of the patients. These
included leptomeningeal contrast enhancement and evidence of meningeal-based
lesions sometimes masquerading as intraparenchymal lesions. Despite
aggressive systemic and local treatment, the outcome was poor, reflecting
the aggressiveness of the underlying MM. CONCLUSION: Leptomeningeal
myelomatosis, although rare, should be considered in patients with MM and
symptoms suggestive of widespread nervous system involvement.
PMID: 15364689 [PubMed - indexed for MEDLINE]
-
| 7: Cancer Res. 2004 Oct 1;64(19):7011-21.■ |
|
-
Isolation and characterization of tumorigenic, stem-like
neural precursors from human glioblastoma.
Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco
R, Foroni C, Dimeco F, Vescovi A.
Stem Cell Research Institute and Laboratory of Molecular Diagnostics, H. S.
Raffaele, Milan, Italy.
Transformed stem cells have been isolated from some human cancers. We report
that, unlike other brain cancers, the lethal glioblastoma multiforme
contains neural precursors endowed with all of the critical features
expected from neural stem cells. Similar, yet not identical, to their normal
neural stem cell counterpart, these precursors emerge as unipotent
(astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial)
in culture. More importantly, these cells can act as tumor-founding cells
down to the clonal level and can establish tumors that closely resemble the
main histologic, cytologic, and architectural features of the human disease,
even when challenged through serial transplantation. Thus, cells possessing
all of the characteristics expected from tumor neural stem cells seem to be
involved in the growth and recurrence of adult human glioblastomas
multiforme.
PMID: 15466194 [PubMed - in process]
-
| 8: Cancer Res. 2004 Oct 1;64(19):6892-9. |
|
-
Genetic pathways to glioblastoma: a population-based
study.
Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL,
Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P,
Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P.
International Agency for Research on Cancer, Lyon, France. ohgaki@iarc.fr
We conducted a population-based study on glioblastomas in the Canton of
Zurich, Switzerland (population, 1.16 million) to determine the frequency of
major genetic alterations and their effect on patient survival. Between 1980
and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000
population/year, adjusted to the World Standard Population, was 3.32 in
males and 2.24 in females. Observed survival rates were 42.4% at 6 months,
17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger
patients survived significantly longer, ranging from a median of 8.8 months
(<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH)
10q was the most frequent genetic alteration (69%), followed by EGFR
amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and
PTEN mutations (24%). LOH 10q occurred in association with any of the other
genetic alterations and was predictive of shorter survival. Primary (de
novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that
progressed from low-grade or anaplastic gliomas were rare (5%). Secondary
glioblastomas were characterized by frequent LOH 10q (63%) and TP53
mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were
in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations
were more equally distributed. G:C-->A:T mutations at CpG sites were more
frequent in secondary than primary glioblastomas (56% versus 30%; P =
0.0208). This suggests that the acquisition of TP53 mutations in these
glioblastoma subtypes occurs through different mechanisms.
PMID: 15466178 [PubMed - in process]
-
| 9: Cancer Res. 2004 Oct 1;64(19):6858-62. |
|
-
Convection-enhanced delivery of tumor necrosis
factor-related apoptosis-inducing ligand with systemic administration of
temozolomide prolongs survival in an intracranial glioblastoma xenograft
model.
Saito R, Bringas JR, Panner A, Tamas M, Pieper RO, Berger MS, Bankiewicz
KS.
Brain Tumor Research Center, Department of Neurological Surgery, University
of California at San Francisco, San Francisco, California 94103, USA.
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is
a potent activator of cell death, preferentially killing neoplastic cells
over normal cells, the efficacy of TRAIL for the treatment of glioma might
be limited due to cellular resistance and, importantly, poor distribution
after systemic administration. TRAIL and temozolomide (TMZ) were recently
shown to have a synergistic antitumor effect against U87MG glioma cells in
vitro. Convection-enhanced delivery (CED) can effectively distribute TRAIL
protein throughout a brain tumor mass. In this study, we evaluated CED of
TRAIL, alone and in conjunction with systemic TMZ administration, for
antitumor efficacy. CED of TRAIL demonstrated safe and effective
distribution in both normal brain and a U87MG intracranial xenograft model.
Individually, both CED of TRAIL and systemic TMZ administration prolonged
survival in tumor-bearing rats. However, the combination of these two
treatments was significantly more effective than either treatment alone. CED
of TRAIL in conjunction with systemic TMZ treatment is a promising strategy
for the treatment of malignant gliomas.
PMID: 15466173 [PubMed - in process]
-
| 10: Cancer Res. 2004 Oct 1;64(19):6845-8. |
|
-
Schedule-dependent inhibition of hypoxia-inducible
factor-1alpha protein accumulation, angiogenesis, and tumor growth by
topotecan in U251-HRE glioblastoma xenografts.
Rapisarda A, Zalek J, Hollingshead M, Braunschweig T, Uranchimeg B,
Bonomi CA, Borgel SD, Carter JP, Hewitt SM, Shoemaker RH, Melillo G.
Science Applications International Corporation-Frederick, Inc., National
Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
melillog@ncifcrd.gov
We have previously shown that topotecan, a topoisomerase I poison, inhibits
hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA
damage-independent mechanism. Here, we report that daily administration of
topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma
xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a
significant tumor growth inhibition associated with a marked decrease of
angiogenesis and expression of HIF-1 target genes in tumor tissue. These
results provide a compelling rationale for testing topotecan in clinical
trials to target HIF-1 in cancer patients.
PMID: 15466170 [PubMed - in process]
-
| 11: Clin Cancer Res. 2004 Mar 1;10(5):1780-8. |
|
-
Molecular pathology shows p16 methylation in
nonadenomatous pituitaries from patients with Cushing's disease.
Simpson DJ, McNicol AM, Murray DC, Bahar A, Turner HE, Wass JA, Esiri MM,
Clayton RN, Farrell WE.
Institute of Science and Technology in Medicine, School of Medicine, Keele
University, Stoke on Trent, Staffordshire, United Kingdom.
PURPOSE: The majority of cases of Cushing's disease are due to the presence
of a corticotroph microadenoma. Less frequently no adenoma is found and
histology shows either corticotroph hyperplasia, or apparently normal
pituitary. In this study we have used molecular pathology to determine
whether the tissue labeled histologically as "normal" is indeed
abnormal. EXPERIMENTAL DESIGN: Tissue from 31 corticotroph adenomas and 16
nonadenomatous pituitaries were subject to methylation-sensitive PCR to
determine the methylation status of the p16 gene CpG island. The proportion
of methylated versus unmethylated CpG island was determined using combined
bisulphite restriction analysis. Methylation status was correlated with
immunohistochemical detection of p16. RESULTS: Seventeen of 31 adenomas
(54.8%), 4 of 6 cases of corticotroph hyperplasia, and 7 of 10 apparently
normal pituitaries showed p16 methylation. Ten of 14 (71%; P = 0.01)
adenomas and 2 of 3 cases of corticotroph hyperplasia, which were
methylated, failed to express p16 protein. However, only 2 of 7 apparently
normal pituitaries that were methylated failed to express p16 protein.
Quantitative analysis of methylation using combined bisulphite restriction
analysis showed only unmethylated CpG islands in postmortem normal
pituitaries; however, in adenomas 80-90% of the cells within a specimen were
methylated. The reverse was true for corticotroph hyperplasia and apparently
normal pituitaries where only 10-20% of the cells were methylated. Thus, the
decreased proportion of cells that were methylated, particularly in those
cases of apparently normal pituitary, is the most likely explanation for the
lack of association between this change and loss of cognate protein in these
cases. CONCLUSIONS: To our knowledge this is the first report that describes
an intrinsic molecular change, namely methylation of the p16 gene CpG
island, common to all three histological patterns associated with Cushing's
disease. Thus, the use of molecular pathology reveals abnormalities
undetected by routine pathological investigation. In cases of
"apparently" normal pituitaries it is not possible to determine
whether the change is associated with adenoma cells "scattered"
throughout the gland, albeit few in number, or with the ancestor-clonal
origin of these tumor cells.
PMID: 15014032 [PubMed - indexed for MEDLINE]
-
| 12: Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):853-60. |
|
Randomized comparison of stereotactic radiosurgery
followed by conventional radiotherapy with carmustine to conventional
radiotherapy with carmustine for patients with glioblastoma multiforme:
Report of Radiation Therapy Oncology Group 93-05 protocol.
Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig
R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran
WJ Jr.
Department of Oncology, Division of Radiation Oncology, McGill University,
Montreal, Canada.
PURPOSE: Conventional treatment of glioblastoma multiforme (GBM) cures less
than 5% of patients. We investigated the effect of stereotactic radiosurgery
(SRS) added to conventional external beam radiation therapy (EBRT) with
carmustine (BCNU) on the survival of patients with GBM. METHODS AND
MATERIALS: A total of 203 patients with supratentorial GBM (tumor <==40
mm) were randomly assigned either to postoperative SRS followed by EBRT (60
Gy) plus BCNU (80 mg/m(2) Days 1-3 every 8 weeks for six cycles) or to EBRT
with BCNU alone. The dose of radiosurgery was tumor size-dependent and
ranged from 15 Gy for largest to 24 Gy for smallest tumors. RT and BCNU were
identical in both arms. RESULTS: At a median follow-up time of 61 months,
the median survival in the radiosurgery group was 13.5 months (95%
confidence interval, 11.0-14.8) as compared with 13.6 months (95% confidence
interval, 11.2-15.2, p = 0.5711) for the standard treatment group. There
were also no significant differences in 2- and 3-year survival rates and in
patterns of failure between the two arms. Quality of life deterioration and
cognitive decline at the end of therapy, compared with baseline, were
comparable and there was no difference in quality-adjusted survival between
the arms. CONCLUSIONS: Stereotactic radiosurgery followed by EBRT and BCNU
does not improve the outcome in patients with GBM nor does it change the
general quality of life or cognitive functioning.
PMID: 15465203 [PubMed - in process]
-
| 13: Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):214-7. |
|
-
Impact of margin for target volume in low-dose involved
field radiotherapy after induction chemotherapy for intracranial germinoma.
Shirato H, Aoyama H, Ikeda J, Fujieda K, Kato N, Ishi N, Miyasaka K,
Iwasaki Y, Sawamura Y.
Departments of Radiology, Neurosurgery, and Pediatrics, Hokkaido University
School of Medicine, North-15 West-7, Kita-ku, Sapporo 060-8638, Japan.
hshirato@radi.med.hokudai.ac.jp
PURPOSE: We previously published a report stating that germinomas with
elevated serum beta human chorionic gonadotropin (HCG-beta) had a poor
relapse rate, but these findings have not been supported by a
multi-institutional trial. The margin for initial gross tumor volume (GTV)
before surgery and chemotherapy of the same materials was investigated by
retrospective review. METHODS AND MATERIAL: The 27 patients reported on in
the previous paper were analyzed. The two-dimensional margin from the
initial GTV to 90% of the prescribed dose of 24 Gy was 2.0 cm for a solitary
lesion in the protocol. This margin was measured retrospectively without
knowledge of the serum HCG-beta level. The whole ventricle field was used
for patients with multifocal disease and whole central nervous system field
was used for disseminated disease, respectively. RESULTS: Six relapses were
seen in 18 patients with solitary tumors, and were treated with the minimum
margin of 1.5 cm or less to the initial GTV. Five of the 6 had initially
elevated serum HCG-beta at the median of 7.4 mIU/mL, ranging from 0.7-233
mIU/mL. No relapses were seen in the 9 patients who were treated with whole
ventricle or whole central nervous system field. CONCLUSIONS: An inadequate
margin and elevated serum HCG-beta were equally determined to be candidates
that caused the poor local control. The whole ventricle is recommended as
the smallest target volume for germinoma with or without elevated HCG-beta
after induction chemotherapy.
PMID: 15337558 [PubMed - indexed for MEDLINE]
-
| 14: Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):204-13. |
|
-
Patterns of failure in supratentorial primitive
neuroectodermal tumors treated in Children's Cancer Group Study 921, a phase
III combined modality study.
Hong TS, Mehta MP, Boyett JM, Donahue B, Rorke LB, Yao MS, Zeltzer PM.
Department of Human Oncology, University of Wisconsin School of Medicine,
Madison, WI, USA.
PURPOSE: To analyze the patterns of failure in patients with supratentorial
primitive neuroectodermal tumors (ST-PNETs) treated with combined modality
therapy in a large, randomized, multi-institutional study. METHODS AND
MATERIALS: A total of 44 prospectively staged patients with ST-PNET
confirmed by central pathology review were treated in the Children's Cancer
Group Study 921, which compared two chemoradiotherapy regimens. The patterns
of initial sites of failure were analyzed. These were compared with the
failure patterns of 188 children with posterior fossa (PF) PNETs treated in
the same protocol. RESULTS: The major determinant for progression-free
survival was the initial metastatic stage. The 3-year progression-free
survival for M0 patients was 53% +/- 8.5% compared with 14% +/- 9.4% for M+
patients. The cumulative 5-year relapse incidence was 71.4% +/- 21% for M+
patients compared with 47.5% +/- 8.6% for M0 patients. The overall failure
rate for both M0 and M+ ST-PNETs was greater than that for PF-PNETs (47.5%
+/- 8.6% vs. 29.3% +/- 4.7% for M0 and 71.4% +/- 21% vs. 48.4% +/- 5.5% for
M+). Failure at the primary site, either as the sole site or as a component
of initial failure, was also seen more frequently in ST-PNETs than in
PF-PNETs. For M0 patients, the 5-year local failure rate as a component of
initial failure was 42.0% +/- 8.5% for ST-PNETs compared with 17.7% +/- 3.9%
for PF-PNETs. For patients with primary tumors either in the ST or PF, the
5-year spinal axis failure rate as a component of initial failure was not
significantly different statistically when compared by M stage. For M+
patients, the 5-year spinal axis failure rate as a component of initial
failure was 42.9% +/- 22.8% for ST-PNETs and 34.6% +/- 5.2% for PF-PNETs.
CONCLUSION: Despite aggressive combined modality therapy, ST-PNETs had high
rates of failure, with M+ patients faring especially poorly. Both local and
spinal failure rates remained high, indicating the need to maximize both
local and regional/systemic therapies. Overall, these patients fared worse
than those with high-risk PF-PNETs in terms of progression-free survival and
failure rates.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase III
- Multicenter Study
- Randomized Controlled Trial
PMID: 15337557 [PubMed - indexed for MEDLINE]
-
| 15: J Nucl Med. 2004 Oct;45(10):1776-1783. |
|
-
Pegylated Arg-Gly-Asp Peptide: 64Cu Labeling and PET
Imaging of Brain Tumor {alpha}v{beta}3-Integrin Expression.
Chen X, Hou Y, Tohme M, Park R, Khankaldyyan V, Gonzales-Gomez I, Bading
JR, Laug WE, Conti PS.
PET Imaging Science Center, Keck School of Medicine, University of Southern
California, Los Angeles, California.
The alpha(v)-integrins, cell adhesion molecules that are highly expressed on
activated endothelial cells and tumor cells but not on dormant endothelial
cells or normal cells, present an attractive target for tumor imaging and
therapy. We previously coupled a cyclic Arg-Gly-Asp (RGD) peptide, c(RGDyK),
with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)
and labeled the RGD-DOTA conjugate with (64)Cu (half-life, 12.8 h; 19%
beta(+)) for solid tumor targeting, with high tumor-to-background contrast.
The rapid tumor washout rate and persistent liver and kidney retention of
this tracer prompted us to optimize the tracer for improved pharmacokinetic
behavior. In this study, we introduced a polyethylene glycol (PEG; molecular
weight, 3,400) moiety between DOTA and RGD and evaluated the
(64)Cu-DOTA-PEG-RGD tracer for microPET imaging in brain tumor models.
METHODS: DOTA was activated in situ and conjugated with RGD-PEG-NH(2) under
slightly basic conditions. alpha(v)beta(3)-Integrin-binding affinity was
evaluated with a solid-phase receptor-binding assay in the presence of
(125)I-echistatin. Female nude mice bearing subcutaneous U87MG glioblastoma
xenografts were administered (64)Cu-DOTA-PEG-RGD, and the biodistributions
of the radiotracer were evaluated from 30 min to 4 h after injection.
microPET (20 min of static imaging at 1 h after injection) and then
quantitative autoradiography were used for tumor visualization and
quantification. The same tracer was also applied to an orthotopic U87MG
model for tumor detection. RESULTS: The radiotracer was synthesized with a
high specific activity (14,800-29,600 GBq/mmol [400-800 Ci/mmol]). The
c(RGDyK)-PEG-DOTA ligand showed intermediate binding affinity for
alpha(v)beta(3)-integrin (50% inhibitory concentration, 67.5 +/- 7.8 nmol/L
[mean +/- SD]). The pegylated RGD peptide demonstrated rapid blood clearance
(0.57 +/- 0.15 percentage injected dose [%ID]/g [mean +/- SD] at 30 min
after injection and 0.03 +/- 0.02 %ID/g at 4 h after injection). Activity
accumulation in the tumor was rapid and high at early time points (2.74 +/-
0.45 %ID/g at 30 min after injection), and some activity washout was seen
over time (1.62 +/- 0.18 %ID/g at 4 h after injection). Compared with
(64)Cu-DOTA-RGD, this tracer showed improved in vivo kinetics, with
significantly reduced liver uptake (0.99 +/- 0.08 %ID/g vs. 1.73 +/- 0.39
%ID/g at 30 min after injection and 0.58 +/- 0.07 %ID/g vs. 2.57 +/- 0.49
%ID/g at 4 h after injection). The pegylated RGD peptide showed higher renal
accumulation at early time points (3.51 +/- 0.24 %ID/g vs. 2.18 +/- 0.23
%ID/g at 30 min after infection) but more rapid clearance (1.82 +/- 0.29
%ID/g vs. 2.01 +/- 0.25 %ID/g at 1 h after injection) than (64)Cu-DOTA-RGD.
The integrin receptor specificity of this radiotracer was demonstrated by
blocking of tumor uptake by coinjection with nonradiolabeled c(RGDyK). The
high tumor-to-organ ratios for the pegylated RGD peptide tracer (at 1 h
after injection: tumor-to-blood ratio, 20; tumor-to-muscle ratio, 12;
tumor-to-liver ratio, 2.7; and tumor-to-kidney ratio, 1.2) were confirmed by
microPET and autoradiographic imaging in a subcutaneous U87MG tumor model.
This tracer was also able to detect an orthotopic brain tumor in a model in
which U87MG cells were implanted into the mouse forebrain. Although the
magnitude of tumor uptake in the orthotopic xenograft was lower than that in
the subcutaneous xenograft, the orthotopic tumor was still visualized with
clear contrast from normal brain tissue. CONCLUSION: This study demonstrated
the suitability of a PEG moiety for improving the in vivo kinetics of a
(64)Cu-RGD peptide tracer without compromising the tumor-targeting ability
and specificity of the peptide. Systematic investigations of the effects of
the size and geometry of PEG on tumor targeting and in vivo kinetics will
lead to the development of radiotracers suitable for clinical applications
such as visualizing and quantifying alpha(v)-integrin expression by PET. In
addition, the same ligand labeled with therapeutic radionuclides may be
applicable for integrin-targeted internal radiotherapy.
PMID: 15471848 [PubMed - as supplied by publisher]
-
| 16: J Nucl Med. 2004 Oct;45(10):1653-9. |
|
-
18F-FDG PET of Gliomas at Delayed Intervals: Improved
Distinction Between Tumor and Normal Gray Matter.
Spence AM, Muzi M, Mankoff DA, O'sullivan SF, Link JM, Lewellen TK,
Lewellen B, Pham P, Minoshima S, Swanson K, Krohn KA.
Department of Neurology, University of Washington School of Medicine,
Seattle, Washington.
We hypothesized that delineation of gliomas from gray matter with (18)F-FDG
PET could be improved by extending the interval between (18)F-FDG
administration and PET data acquisition. The purposes of this study were,
first, to analyze standard and delayed (18)F-FDG PET images visually and
quantitatively to determine whether definition of tumor improved at later
imaging times and, second, to investigate the dynamics of model-derived
kinetic rate constants, particularly k4. METHODS: Nineteen adult patients
with supratentorial gliomas were imaged from 0 to 90 min and once or twice
later at 180-480 min after injection. In 15 patients, arterial sampling
provided the early input function. Venous sampling provided the remaining
curve to the end of the imaging sequence. Standardized uptake value (SUV)
was calculated as tissue concentration of tracer per injected tracer dose
per body weight. Ratios of tumor SUV relative to the SUV of gray matter,
brain (including gray and white matter), or white matter were calculated at
each imaging time point. Dynamic image data from tumor, gray matter, brain,
or white matter were analyzed using a 2-compartment, 4-parameter model
applied for the entire duration of imaging, in which delay, K1, distribution
volume, k3, and k4 were optimized using a nonlinear optimization method.
Parameter estimation for each region included both an early subset of data
from a conventional dynamic imaging period (0-60 min) and the full, extended
dataset for each region. RESULTS: In 12 of the 19 patients, visual analysis
showed that the delayed images better distinguished the high uptake in
tumors relative to uptake in gray matter. SUV comparisons also showed
greater uptake in the tumors than in gray matter, brain, or white matter at
the delayed times. The estimated k4 values for tumors were not significantly
different from those for gray matter in early imaging analysis but were
lower (P < 0.01) using the extended-time data. CONCLUSION: The kinetic
parameter results confirm the visual and SUV interpretation that tumor
enhancement is greater than enhancement of surrounding brain regions at
later imaging times, consistent with a greater effect of FDG-6-phosphate
degradation on normal brain relative to glioma.
PMID: 15471829 [PubMed - in process]
|
Volume 3, Supplement 6 - 12
October 2004