2. Academic Validation
  3. 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

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

  • Bioorg Med Chem. 2014 Mar 1;22(5):1700-7. doi: 10.1016/j.bmc.2014.01.019.
Dong Zhou 1,  Wenhua Chu 1,  Jinbin Xu 1,  Lynne A Jones 1,  Xin Peng 1,  Shihong Li 1,  Delphine L Chen 1,  Robert H Mach 2
Affiliations

Affiliations

  • 1 Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
  • 2 Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA. Electronic address: rmach@mail.med.upenn.edu.
PMID: 24503274 DOI: 10.1016/j.bmc.2014.01.019
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 (18)F-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). [(18)F]12 was synthesized under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET studies using [(18)F]12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [(18)F]12 in the tumor that was blocked by olaparib, suggesting that the uptake of [(18)F]12 in the tumor is specific to PARP-1 expression.

Keywords

Imaging; PARP-1; PET; Radiolabeling.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-164475
    PARP-1 Inhibitor