Development of a (177)Lu-Labeled RGD Derivative for Targeting Angiogenesis

Abstract

Various Arg-Gly-Asp (RGD) derivatives have been labeled with various radioisotopes for targeting alpha(v)beta(3) integrin, which is expressed during angiogenesis in tumor. In this study, 2-(4`-isothiocyanatobenzyl)-1,4,7-triazacyclononane- 1,4,7-triacetic acid (NOTA-SCN) and its c(RGDyK) conjugate (NOTA-SCN-c(RGDyK)) were labeled with (177)Lu, which is a near ideal radionuclide for treating tumors because it emits therapeutic beta particles and gamma rays for monitoring. (177)Lu (250 MBq) was labeled with 50 mu g NOTA-SCN-c(RGDyK) quantitatively. The specific activity of (177)Lu-NOTA-SCN-c(RGDyK) was 1.44 X 10(5) Ci/mol. Biodistribution study was performed in Balb/c mice xenografted with CT-26 (mouse colon cancer) cells. The highest uptake was found in kidneys (7.56% +/- 0.71% ID/g at 1 hour), and tumor uptake was 1.70% +/- 0.33% ID/g at 1 hour postinjection. Moderate tumor-to-blood (2.36 +/- 0.29) and tumor-to-muscle (2.06 +/- 0.40) ratios were observed. This study shows that (177)Lu-NOTA-SCN-c(RGDyK) is a potential therapeutic agent for angiogenic tumors, but special care is required to prevent kidney toxicity.