68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides

Mol Pharm. 2021 Sep 6;18(9):3553-3562. doi: 10.1021/acs.molpharmaceut.1c00460. Epub 2021 Aug 17.

Abstract

Probes for radiotheranostics could be produced by introducing radionuclides with similar chemical characteristics into the same precursors. We recently developed an 211At-labeled RGD peptide and a corresponding radioiodine-labeled RGD peptide. Both labeled peptides accumulated in large quantities in the tumor with similar biodistribution, demonstrating their usefulness for radiotheranostics. In this study, we hypothesized that probes for radiotheranostics combined with multiradionuclides, such as 68Ga and 211At, have useful clinical applications. New radiolabeled RGD peptide probes were synthesized via a molecular design approach, with two labeling sites for metal and halogen. These probes were evaluated in biodistribution experiments using tumor-bearing mice. [67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]4), Ga-DOTA-[125I]c[RGDf(4-I)K] ([125I]4), and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]7) showed similar biodistribution, with high and equivalent accumulation in tumors. These results indicate the usefulness of these probes in radiotheranostics with multiradionuclides, such as a radiometal and a radiohalogen, and they could contribute to a personalized medicine regimen.

Keywords: RGD peptide; astatine-211; gallium-68; multiradionuclides; radiotheranostics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astatine
  • Cell Line, Tumor
  • Drug Stability
  • Gallium Radioisotopes
  • Humans
  • Mice
  • Neoplasms / diagnostic imaging*
  • Neoplasms / pathology
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Astatine-211
  • Gallium Radioisotopes
  • Oligopeptides
  • Radiopharmaceuticals
  • Gallium-67
  • arginyl-glycyl-aspartic acid
  • Astatine