Département de chimie moléculaire

{64Cu-cyclam-RAFT-c(-RGDfK-)4 is a novel multimeric positron emission tomog. (PET) probe for $\alpha$V$\beta$3 integrin imaging. Its uptake and $\alpha$V$\beta$3 expression in tumors showed a linear correlation. Since $\alpha$V$\beta$3 integrin is strongly expressed on activated endothelial cells during angiogenesis, we aimed to det. whether 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET can be used to image tumor angiogenesis and monitor the antiangiogenic effect of a novel multi-targeted tyrosine kinase inhibitor, TSU-68. Athymic nude mice bearing human hepatocellular carcinoma HuH-7 xenografts, which expressed negligible $\alpha$V$\beta$3 levels on the tumor cells, received i.p. injections of TSU-68 or the vehicle for 14 days. Antiangiogenic effects were detd. at the end of therapy in terms of 64Cu-cyclam-RAFT-c(-RGDfK-)4 uptake evaluated using PET, biodistribution assay, and autoradiog., and they were compared with microvessel d. (MVD) detd. by CD31 immunostaining. 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET enabled clear tumor visualization by targeting the vasculature, and the biodistribution assay indicated high tumor-to-blood and tumor-to-muscle ratios of 31.6 ± 6.3 and 6.7 ± 1.1, resp., 3 h after probe injection. TSU-68 significantly slowed tumor growth and reduced MVD; these findings were consistent with a significant redn. in the tumor 64Cu-cyclam-RAFT-c(-RGDfK-)4 uptake. Moreover, a linear correlation was obsd. between tumor MVD and the corresponding standardized uptake value (SUV) (r = 0.829