Noninvasive imaging of α _v β ₃ integrin expression using ¹⁸ F-labeled RGD-containing glycopeptide and positron emission tomography

The α _v β ₃ integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the ¹⁸ F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[ ¹⁸ F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized α _v β ₃ , α _v β ₅ , and α _IIb β ₃ as well as in vivo studies using α _v β ₃ -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 α _v β ₃ integrin status and therapy monitoring.