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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Structures / metabolism
  • Animals
  • Chelating Agents / chemistry
  • Chromatography, High Pressure Liquid
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / radiotherapy*
  • Drug Delivery Systems / methods
  • Drug Stability
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds, 1-Ring
  • Kidney / metabolism
  • Lutetium / administration & dosage*
  • Lutetium / chemistry
  • Lutetium / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Neovascularization, Pathologic / radiotherapy*
  • Oligopeptides / chemistry*
  • Radioisotopes / administration & dosage
  • Radioisotopes / chemistry
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Tissue Distribution

Substances

  • Chelating Agents
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Oligopeptides
  • Radioisotopes
  • Radiopharmaceuticals
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Lutetium
  • arginyl-glycyl-aspartic acid