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Noninvasive
estimation of tumour viability in a xenograft model of human
neuroblastoma with proton magnetic resonance spectroscopy (1H
MRS) M
Lindskog, P Kogner, F Ponthan, P Schweinhardt, B Sandstedt, T Heiden,
G Helms and C Spenger
Childhood
Cancer Research Unit, Department of Woman and Child Health, Karolinska
Institutet, Karolinska Hospital, S-171 76 Stockholm, Sweden
[M.L., P.K., F.P., B.S.]. MR-Centre,
Department of Clinical Neuroscience and Department of Neuroscience,
Karolinska Institutet S-171 76 Stockholm, Sweden
[P.S., G.H., C.S.]. Research Group Tumor Genetics and Molecular
Genetics, Institute of Medical Genetics, Charite, Humboldt University
of Berlin, Germany
[T.H.]. Correspondence to: Dr P Kogner,
Childhood Cancer Research Unit, Department of Woman and Child Health,
Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm,
Sweden. E-mail: Per.Kogner@ks.se
.Received
15 July 2002; revised 7 October 2002; accepted 7 October 2002.
The
aim of the study was to evaluate proton magnetic resonance
spectroscopy (1H MRS) for noninvasive biological
characterisation of neuroblastoma xenografts in vivo.
For
designing the experiments, human neuroblastoma xenografts growing
subcutaneously in nude rats were analysed in vivo with 1H
MRS and magnetic resonance imaging at 4.7 T.
The
effects of spontaneous tumour growth and antiangiogenesis treatment,
respectively, on spectral characteristics were evaluated.
The
spectroscopic findings were compared to tumour morphology,
proliferation and viable tumour tissue fraction.
The
results showed that signals from choline (Cho)-containing compounds
and mobile lipids (MLs) dominated the spectra.
The
individual ML/Cho
ratios for both treated and untreated tumours were positively
correlated with tumour volume (P<0.05).
There
was an inverse correlation between the ML/Cho
ratio and the viable tumour fraction (r=-0.86, P<0.001).
Higher
ML/Cho
ratios concomitant with pronounced histological changes were seen in
spectra from tumours treated with the antiangiogenic drug TNP-470,
compared to untreated control tumours (P<0.05).
In
conclusion, the ML/Cho
ratio obtained in vivo by 1H MRS enabled accurate
assessment of the viable tumour fraction in a human neuroblastoma
xenograft model.
1H
MRS also revealed early metabolic effects of antiangiogenesis
treatment.
1H
MRS could prove useful as a tool to monitor experimental therapy in
preclinical models of neuroblastoma, and possibly also in children.
Keywords:
neuroblastoma; xenograft; spectroscopy; MRI; angiogenesis; therapy
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