Article
Monitoring anti-angiogenic treatment by perfusion MRI in an intracerebral glioblastoma model
Perfusions-MRI in einem intrazerebralen Glioblastom-Modell
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Authors
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Nils Ole Schmidt
- Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA; Klinik für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
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Y. Sun
- Department of Radiology, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
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M. Ziu
- Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
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R. S. Carroll
- Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
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P. M. Black
- Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
| Published: | April 23, 2004 |
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Outline
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Objective
Targeting of active angiogenesis which is a major hallmark in many brain tumors, is an attractive adjuvant therapeutic approach. Delivery and scheduling of angiogenesis inhibitors in combination with other therapeutic approaches are of particular importance for the successful clinical integration of anti-angiogenic therapies. In this respect, non invasive MRI-assessed data reflecting pathophysiological changes like tumor blood flow during treatment in a highly reproducible tumor model would help in the development and preclinical evaluation of new anti-angiogenic drugs.
Methods
MRI experiments were performed on a Bruker 8.5 T DRX vertical bore micro-imaging system (Bruker Instruments, Billerica, MA). Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in treated and untreated orthotopic U87 human glioblastoma xenografts. As an anti-angiogenic treatment paradigm, nude mice bearing well-established U87 glioma received daily intraperitoneal injections of a monoclonal antibody against the VEGF-receptor 2 (DC101). Furthermore T2, T1 and Gd-enhanced T1-weighted MR images were obtained.
Results
The mean index of cerebral blood flow (ICBF) in the intracerebral gliomas (n=14) was found to be 50 ± 9 ml/100g/min for tumor core and 209 ± 11 ml/100g/min for normal tissue. The ICBF varied heterogeneously throughout the tumor mass with the tendency to decrease from the periphery to the core of the glioma as demonstrated by color coded perfusion maps and a newly developed radial profile analysis. Our initial results indicated that tumors of animals receiving anti-angiogenic treatment displayed a higher blood flow throughout the tumor mass than those of untreated animals.
Conclusions
Our data support the notion that perfusion MRI can be successfully implemented for assessing the tumor blood flow in an experimental intracerebral glioblastoma model. Treatment effects can be non-invasively monitored over time providing important information for the development of new therapeutic regimens.
