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

作者：Ju Chang Hwan; Jeong Jae Min^*; Lee Yun Sang; Kim Young Joo; Lee Byung Chul; Lee Dong Soo; Chung June Key; Lee Myung Chul; Jeong Seo Young

来源：Cancer Biotherapy and Radiopharmaceuticals, 2010, 25(6): 687-691.

DOI：10.1089/cbr.2010.0825

• angiogenesis
• Lu-177
• lutetium
• NOTA
• radionuclide therapy
• RGD

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 Lu-177, which is a near ideal radionuclide for treating tumors because it emits therapeutic beta particles and gamma rays for monitoring. Lu-177 (250 MBq) was labeled with 50 mu g NOTA-SCN-c(RGDyK) quantitatively. The specific activity of Lu-177-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 Lu-177-NOTA-SCN-c(RGDyK) is a potential therapeutic agent for angiogenic tumors, but special care is required to prevent kidney toxicity.

• 出版日期2010-12