title: 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.
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.
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Dong
authors: D
authors: Zhou
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Wenhua
authors: W
authors: Chu
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Jinbin
authors: J
authors: Xu
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Lynne A
authors: LA
authors: Jones
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Xin
authors: X
authors: Peng
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Shihong
authors: S
authors: Li
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
authors: Delphine L
authors: DL
authors: Chen
authors: Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA. Electronic address: rmach@mail.med.upenn.edu.
authors: Robert H
authors: RH
authors: Mach
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011065:Poly(ADP-ribose) Polymerases
keywords: Imaging; PARP-1; PET; Radiolabeling