title: Development of a ¹⁷⁷Lu-labeled RGD derivative for targeting angiogenesis.
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.
authors.affiliation: Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Ju
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
mesh_terms: D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D007668:Kidney / Q000378:metabolism; D008187:Lutetium / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D009842:Oligopeptides / Q000737:chemistry*; D011868:Radioisotopes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D008187:Lutetium; C047981:arginyl-glycyl-aspartic acid