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First published on April 28, 2009
Neuro Oncol 2009, DOI:10.1215/15228517-2009-024
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© Copyright 2009 by the Society for Neuro-Oncology

Received July 17, 2008
Accepted February 25, 2009

Clinical Investigations

Imaging of integrin {alpha}v{beta}3 expression in patients with malignant glioma by [18F]galacto-RGD positron emission tomography

Oliver Schnell 1, Bjarne Krebs 2, Janette Carlsen 3, Isabelle Miederer 3, Claudia Goetz 1, Roland H. Goldbrunner 1, Hans-Jürgen Wester 3, Roland Haubner 4, Gabriele Pöpperl 5, Markus Holtmannspötter 6, Hans A. Kretzschmar 7, Horst Kessler 8, Jörg-Christian Tonn 9, Markus Schwaiger 10, Ambros J. Beer 3*

1 Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
2 Center for Neuropathology and Prion Research, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
3 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
4 Universitätsklinik für Nuklearmedizin, Medizinische Universität Innsbruck, Austria
5 Department of Nuclear Medicine, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
6 Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
7 Center for Neuropathology and Prion Research, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
8 Center of Integrated Protein Science, Department of Chemistry, Technische Universität München, Garching, Germany
9 Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany
10 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

* To whom correspondence should be addressed. E-mail: beer{at}roe.med.tum.de.


   Abstract

Inhibitors targeting the integrin {alpha}v{beta}3 are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate [18F]Galacto-RGD positron emission tomography (PET) for non-invasive imaging of {alpha}v{beta}3 expression in patients with GBM suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [18F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea and blood pool were derived by region-of-interest analysis. [18F]Galacto-RGD PET images were fused with cranial MRI scans for image guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [18F]Galacto-RGD PET were analyzed histologically and immunhistochemically for {alpha}v{beta}3 integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV 0.09 ± 0.04), GBMs demonstrated significant but heterogeneous tracer uptake with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV 1.6 ± 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [18F]Galacto-RGD PET correlated to the immunohistochemical {alpha}v{beta}3 integrin expression of corresponding tumor samples. These data suggest that [18F]Galacto-RGD PET successfully identifies {alpha}v{beta}3 expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin.

Key Words: malignant glioma, {alpha}v{beta}3, integrins, intellectual impairment, [18F]Galacto-RGD, PET, angiogenesis


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