Monitoring tumor response to ZD4190 therapy with an 18F labeled angiogenesis imaging agent

10507 Background: While a number of novel therapies are being developed to inhibit the growth or survival of tumor vasculature, there are limited methods available for measuring changes in tumor vascularity. In order to quantify tumour vascularity by PET imaging, we examined an 18F-radiolabeled small peptide (AH111585) containing an RGD (Arg-Gly-Asp) sequence. This peptide binds with high affinity (nM) to avβ3 integrin, a cell adhesion receptor that is highly expressed on tumor neovasculature, but expressed at low levels on mature endothelium and epithelial cells. 18F-AH111585 was used to examine the response of human lung tumor xenografts to treatment with ZD4190, a small molecule inhibitor of VEGF signaling. Methods: MicroPET (using 18F-AH111585) and microCT imaging data was acquired pre and post 3 doses of ZD4190 (100 mg/kg, p.o., over 3 days) or vehicle in CD-1 nude mice bearing Calu-6 tumor xenografts. 18F-AH111585 was administered 2 h prior to microPET imaging (10 min) to allow for tumor uptake and ...