Dong Zhou1, Wenhua Chu1, Jinbin Xu1, Lynne A Jones1, Xin Peng1, Shihong Li1, Delphine L Chen1, Robert H Mach2. 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.
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.
Imaging of poly (ADP-ribose) polymerase-1 (n class="Gene">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-436tumor-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: G Gradwohl; J M Ménissier de Murcia; M Molinete; F Simonin; M Koken; J H Hoeijmakers; G de Murcia Journal: Proc Natl Acad Sci U S A Date: 1990-04 Impact factor: 11.205
Authors: Donald J Skalitzky; Joseph T Marakovits; Karen A Maegley; Anne Ekker; Xiao-Hong Yu; Zdenek Hostomsky; Stephen E Webber; Brian W Eastman; Robert Almassy; Jianke Li; Nicola J Curtin; David R Newell; A Hilary Calvert; Roger J Griffin; Bernard T Golding Journal: J Med Chem Date: 2003-01-16 Impact factor: 7.446
Authors: Shahneen K Sandhu; William R Schelman; George Wilding; Victor Moreno; Richard D Baird; Susana Miranda; Lucy Hylands; Ruth Riisnaes; Martin Forster; Aurelius Omlin; Nathan Kreischer; Khin Thway; Heidrun Gevensleben; Linda Sun; John Loughney; Manash Chatterjee; Carlo Toniatti; Christopher L Carpenter; Robert Iannone; Stan B Kaye; Johann S de Bono; Robert M Wenham Journal: Lancet Oncol Date: 2013-06-28 Impact factor: 41.316
Authors: Erin George; Hyoung Kim; Clemens Krepler; Brandon Wenz; Mehran Makvandi; Janos L Tanyi; Eric Brown; Rugang Zhang; Patricia Brafford; Stephanie Jean; Robert H Mach; Yiling Lu; Gordon B Mills; Meenhard Herlyn; Mark Morgan; Xiaochen Zhang; Robert Soslow; Ronny Drapkin; Neil Johnson; Ying Zheng; George Cotsarelis; Katherine L Nathanson; Fiona Simpkins Journal: JCI Insight Date: 2017-01-12
Authors: Giuseppe Carlucci; Brandon Carney; Christian Brand; Susanne Kossatz; Christopher P Irwin; Sean D Carlin; Edmund J Keliher; Wolfgang Weber; Thomas Reiner Journal: Mol Imaging Biol Date: 2015-12 Impact factor: 3.488
Authors: Loren S Michel; Samantha Dyroff; Frank J Brooks; Katherine J Spayd; Sora Lim; Jacquelyn T Engle; Sharon Phillips; Benjamin Tan; Andrea Wang-Gillam; Christopher Bognar; Wenhua Chu; Dong Zhou; Robert H Mach; Richard Laforest; Delphine L Chen Journal: Radiology Date: 2016-11-14 Impact factor: 11.105
Authors: Mehran Makvandi; Austin Pantel; Lauren Schwartz; Erin Schubert; Kuiying Xu; Chia-Ju Hsieh; Catherine Hou; Hyoung Kim; Chi-Chang Weng; Harrison Winters; Robert Doot; Michael D Farwell; Daniel A Pryma; Roger A Greenberg; David A Mankoff; Fiona Simpkins; Robert H Mach; Lilie L Lin Journal: J Clin Invest Date: 2018-04-16 Impact factor: 14.808
Authors: Brandon Carney; Giuseppe Carlucci; Beatriz Salinas; Valentina Di Gialleonardo; Susanne Kossatz; Axel Vansteene; Valerie A Longo; Alexander Bolaender; Gabriela Chiosis; Kayvan R Keshari; Wolfgang A Weber; Thomas Reiner Journal: Mol Imaging Biol Date: 2016-06 Impact factor: 3.488
Authors: Christine E Edmonds; Mehran Makvandi; Brian P Lieberman; Kuiying Xu; Chenbo Zeng; Shihong Li; Catherine Hou; Hsiaoju Lee; Roger A Greenberg; David A Mankoff; Robert H Mach Journal: Am J Nucl Med Mol Imaging Date: 2016-01-28