Synthesis, [18F] radiolabeling, and evaluation of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors for in vivo imaging of PARP-1 using positron emission tomography

Dong Zhou, Wenhua Chu, Jinbin Xu, Lynne A. Jones, Xin Peng, Shihong Li, Delphine L. Chen, Robert H. Mach

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Imaging of poly (ADP-ribose) polymerase-1 (PARP-1) expression in vivo is a potentially powerful tool for developing PARP-1 inhibitors for drug discovery and patient care. We have synthesized several derivatives of benzimidazole carboxamide as PARP-1 inhibitors, which can be 18F-labeled easily for positron emission tomographic (PET) imaging. Of the compounds synthesized, 12 had the highest inhibition potency for PARP-1 (IC50 = 6.3 nM). [ 18F]12 was synthesized under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET studies using [ 18F]12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [18F]12 in the tumor that was blocked by olaparib, suggesting that the uptake of [18F]12 in the tumor is specific to PARP-1 expression.

Original languageEnglish
Pages (from-to)1700-1707
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number5
DOIs
StatePublished - Mar 1 2014

Keywords

  • Imaging
  • PARP-1
  • PET
  • Radiolabeling

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