Synthesis and evaluation of an (125)I-labeled azide prosthetic group for efficient and bioorthogonal radiolabeling of cyclooctyne-group containing molecules using copper-free click reaction

Bioorg Med Chem Lett. 2016 Feb 1;26(3):875-878. doi: 10.1016/j.bmcl.2015.12.073. Epub 2015 Dec 22.

Abstract

Herein we report the radiosynthesis of a pyridine derived azide prosthetic group for iodine radioisotope labeling of dibenzocyclooctyne (DBCO) conjugated molecules. The radiolabeling of the stannylated precursor 2 was conducted using [(125)I]NaI and chloramine-T to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (72±8%, n=4) and radiochemical purity (>99%). Using (125)I-labeled azide ([(125)I]1), cyclic RGD peptide and near infrared fluorescent molecule were efficiently labeled with modest to good radiochemical yields. The biodistribution study and SPECT/CT images showed that [(125)I]1 underwent rapid renal clearance. These results clearly demonstrated that [(125)I]1 could be used as an useful radiotracer for in vivo pre-targeted imaging as well as efficient in vitro radiolabeling of DBCO containing molecules.

Keywords: Biodistribution; Copper-free click reaction; In vivo imaging; Iodine radioisotope; Radiolabeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Animals
  • Azides / chemistry*
  • Click Chemistry*
  • Copper / chemistry
  • Iodine Radioisotopes / chemistry
  • Isotope Labeling
  • Mice
  • Mice, Inbred ICR
  • Oligopeptides / chemistry
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Alkynes
  • Azides
  • Iodine Radioisotopes
  • Oligopeptides
  • Radiopharmaceuticals
  • Copper
  • arginyl-glycyl-aspartic acid