Département de chimie moléculaire

Purpose: The $\alpha$v$\beta$3 integrin plays an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the $\alpha$v$\beta$3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabeled with $\beta$- emitters in a nude mouse model of $\alpha$v$\beta$3 integrin-expressing tumors. Methods: Biodistribution and SPECT/CT imaging studies were performed after injection of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in nude mice s.c. xenografted with $\alpha$v$\beta$3 integrin-expressing U-87 MG cells. Exptl. targeted radionuclide therapy with 90Y-RAFT-RGD or 177Lu-RAFT-RGD and 90Y-RAFT-RAD or 177Lu-RAFT-RAD (nonspecific controls) was evaluated by i.v. injection of the radionuclides into mice bearing $\alpha$v$\beta$3 integrin-expressing U-87 MG tumors of different sizes (small or large) or bearing TS/A-pc tumors that do not express $\alpha$v$\beta$3. Tumor vol. doubling time was used to evaluate the efficacy of each treatment. Results: Injection of 37 MBq of 90Y-RAFT-RGD into mice with large $\alpha$v$\beta$3-pos. tumors or 37 MBq of 177Lu-RAFT-RGD into mice with small $\alpha$v$\beta$3-pos. tumors caused significant growth delays compared to mice treated with 37 MBq of 90Y-RAFT-RAD or 37 MBq of 177Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of 90Y-RAFT-RGD had no effect on the growth of $\alpha$v$\beta$3-neg. tumors. Conclusion: 90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent agents targeting $\alpha$v$\beta$3-expressing tumors for internal targeted radiotherapy. [on SciFinder(R)]