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Noninvasive Imaging of _vß₃ Integrin Expression Using ¹⁸F-labeled RGD-containing Glycopeptide and Positron Emission Tomography¹

Department of Nuclear Medicine, Technische Universität München, 81675 München, Germany [R. H., H-J. W., W. A. W., S. I. Z., R. S-S., M. S.]; Institute of Organic Chemistry and Biochemistry, Technische Universität München, 85747 Garching, Germany [C. M., H. K.]; and Department of Preclinical Oncology, Merck KGaA, 64271 Darmstadt, Germany [S. L. G.]

The _vß₃ integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the ¹⁸F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[¹⁸F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized _vß₃, _vß₅, and _IIbß₃ as well as in vivo studies using _vß₃-positive and -negative murine and xenotransplanted human tumors demonstrated receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios (e.g., 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the _vß₃ integrin status and therapy monitoring.

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