Noninvasive Imaging of avb3 Integrin Expression Using F-labeled RGD-containing Glycopeptide and Positron Emission Tomography

The avb3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-DPhe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized avb3, avb5, and aIIbb3 as well as in vivo studies using avb3-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 avb3 integrin status and therapy monitoring.