Radiosynthesis and evaluation of IGF1R PET ligand [11C]GSK1838705A

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2895-2897. doi: 10.1016/j.bmcl.2017.04.085. Epub 2017 Apr 27.

Abstract

Radiosynthesis and evaluation of [11C]GSK1838705A in mice using microPET and determination of specificity in human GBM UG87MR cells are described herein. The radioligand was synthesized by reacting desmethyl-GSK1838705A with [11C]CH3I using GE FX2MeI module in ∼5% yield (EOS), >95% radiochemical purity and a specific activity of 2.5±0.5Ci/μmol. MicroPET imaging in mice indicated that [11C]GSK1838705A penetrated blood brain barrier (BBB) and showed retention of radiotracer in brain. The radioligand exhibited high uptake in U87MG cells with >70% specific binding to IGF1R. Our experiments suggest that [11C]GSK-1838705A can be a potential PET radiotracer for the in vivo quantification of IGF1R expression in GBM and other brain tumors.

Keywords: Growth factor; IGF1R; Micropet; Radiotracer.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Blood-Brain Barrier / diagnostic imaging
  • Brain / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Carbon Radioisotopes
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Glioblastoma / diagnostic imaging*
  • Humans
  • Mice
  • Molecular Structure
  • Positron-Emission Tomography*
  • Protein Binding
  • Pyrimidines / analysis
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / isolation & purification
  • Pyrimidines / metabolism*
  • Pyrroles / analysis
  • Pyrroles / chemical synthesis*
  • Pyrroles / isolation & purification
  • Pyrroles / metabolism*
  • Radioligand Assay*
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Carbon Radioisotopes
  • GSK 1838705A
  • IGF1R protein, human
  • Pyrimidines
  • Pyrroles
  • Receptors, Somatomedin
  • Receptor, IGF Type 1