开发一种用于靶向血管生成的¹⁷⁷Lu 标记的 RGD 衍生物。

Development of a ¹⁷⁷Lu-labeled RGD derivative for targeting angiogenesis.

机构信息

Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Cancer Biother Radiopharm. 2010 Dec;25(6):687-91. doi: 10.1089/cbr.2010.0825.

DOI:10.1089/cbr.2010.0825

PMID:21204763

Abstract

Abstract Various Arg-Gly-Asp (RGD) derivatives have been labeled with various radioisotopes for targeting α(v)β₃ 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 ¹⁷⁷Lu, which is a near ideal radionuclide for treating tumors because it emits therapeutic beta particles and gamma rays for monitoring. ¹⁷⁷Lu (250 MBq) was labeled with 50 μg NOTA-SCN-c(RGDyK) quantitatively. The specific activity of ¹⁷⁷Lu-NOTA-SCN-c(RGDyK) was 1.44 × 10⁵ 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 ¹⁷⁷Lu-NOTA-SCN-c(RGDyK) is a potential therapeutic agent for angiogenic tumors, but special care is required to prevent kidney toxicity.

摘要

摘要各种 Arg-Gly-Asp（RGD）衍生物已被标记上各种放射性同位素，用于靶向在肿瘤血管生成过程中表达的 α(v)β₃整合素。在这项研究中，2-（4′-异硫氰酸苯甲基）-1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA-SCN）及其 c（RGDyK）缀合物（NOTA-SCN-c（RGDyK））被 ¹⁷⁷Lu 标记，¹⁷⁷Lu 是治疗肿瘤的理想放射性核素，因为它发射治疗β粒子和γ射线以进行监测。定量用 50μg NOTA-SCN-c（RGDyK）标记 ¹⁷⁷Lu（250MBq）。¹⁷⁷Lu-NOTA-SCN-c（RGDyK）的比活度为 1.44×10⁵Ci/mol。在 CT-26（小鼠结肠癌细胞）异种移植的 Balb/c 小鼠中进行了生物分布研究。在 1 小时时，肾脏的摄取最高（7.56%±0.71%ID/g），肿瘤摄取为 1.70%±0.33%ID/g。观察到中等的肿瘤-血液（2.36±0.29）和肿瘤-肌肉（2.06±0.40）比值。这项研究表明，¹⁷⁷Lu-NOTA-SCN-c（RGDyK）是一种有潜力的血管生成肿瘤治疗剂，但需要特别注意以防止肾毒性。