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Clinical Cancer Research Vol. 12, 3942-3949, July 1, 2006
© 2006 American Association for Cancer Research

Imaging, Diagnosis, Prognosis

Positron Emission Tomography Using [18F]Galacto-RGD Identifies the Level of Integrin {alpha}vß3 Expression in Man

Ambros J. Beer1, Roland Haubner9, Mario Sarbia2, Michael Goebel3, Stephan Luderschmidt4, Anca Ligia Grosu5, Oliver Schnell8, Markus Niemeyer6, Horst Kessler7, Hans-Jürgen Wester1, Wolfgang A. Weber10 and Markus Schwaiger1

Authors' Affiliations: Departments of 1 Nuclear Medicine, 2 Pathology, 3 Orthopedic Surgery, 4 Dermatology, 5 Radiation Therapy, and 6 Gynecology and 7 Department Chemie, Lehrstuhl II für Organische Chemie, Technische Universität München; 8 Department of Neurosurgery, Ludwig Maximilians Universität München, Munich, Germany; 9 Universitätsklinik für Nuklearmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria; and 10 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California

Requests for reprints: Ambros J. Beer, Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. Phone: 49-89-4140-2971; Fax: 49-89-4140-4841; E-mail: beer{at}roe.med.tum.de.

Purpose: The integrin {alpha}vß3 plays a key role in angiogenesis and tumor cell metastasis and is therefore an important target for new therapeutic and diagnostic strategies. We have developed [18F]Galacto-RGD, a highly {alpha}vß3-selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [18F]Galacto-RGD uptake correlates with {alpha}vß3 expression.

Experimental Design: Nineteen patients with solid tumors (musculoskeletal system, n = 10; melanoma, n = 4; head and neck cancer, n = 2; gliobastoma, n = 2; and breast cancer, n = 1) were examined with PET using [18F]Galacto-RGD before surgical removal of the tumor lesions. Snap-frozen specimens (n = 26) were collected from representative areas with low and intense standardized uptake values (SUV) of [18F]Galacto-RGD. Immunohistochemistry was done using the {alpha}vß3-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of {alpha}vß3-positive vessels were determined and correlated with SUV and tumor/blood ratios (T/B).

Results: Two tumors showed no tracer uptake (mean SUV, 0.5 ± 0.1). All other tumors showed tracer accumulation with SUVs ranging from 1.2 to 10.0 (mean, 3.8 ± 2.3; T/B, 3.4 ± 2.2; tumor/muscle ratio, 7.7 ± 5.4). The correlation of SUV and T/B with the intensity of immunohistochemical staining (Spearman's r = 0.92; P < 0.0001) as well as with the microvessel density (Spearman's r = 0.84; P < 0.0001) were significant. Immunohistochemistry confirmed lack of {alpha}vß3 expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake.

Conclusions: Molecular imaging of {alpha}vß3 expression with [18F]Galacto-RGD in humans correlates with {alpha}vß3 expression as determined by immunohistochemistry. PET with [18F]Galacto-RGD might therefore be used as a new marker of angiogenesis and for individualized planning of therapeutic strategies with {alpha}vß3-targeted drugs.




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