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

D Zhou, W Chu, J Xu, LA Jones, X Peng, S Li… - Bioorganic & medicinal …, 2014 - Elsevier
D Zhou, W Chu, J Xu, LA Jones, X Peng, S Li, DL Chen, RH Mach
Bioorganic & medicinal chemistry, 2014Elsevier
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 (IC 50= 6.3
nM).[18 F] 12 was synthesized under conventional conditions in high specific activity with 40 …
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.
Elsevier