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 |
| |
| Affiliation: | 1. Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India;2. Department of Chemistry, Pondicherry University, Puducherry 605 014, India;3. Centre for Advance Studies in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605 014, India;1. Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, via Celoria 2, 20133 Milano, Italy;2. R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.,via Pontina Km 30, 400, I-00040 Pomezia (RM), Italy;3. Molecular Pharmacology Unit, Dept. Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, via Amadeo 42, I-20133 Milan, Italy;4. Scientia Advice, di Roberto Artali, 20832 Desio (MB), Italy;1. Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425, Jülich, Germany;2. University of Cologne, Faculty of Medicine and Cologne University Hospital, Center for Neurosurgery, Kerpener Straße 62, 50937, Cologne, Germany;3. University of Cologne, Faculty of Medicine and Cologne University Hospital, Institute of Diagnostic and Interventional Radiology, Kerpener Straße 62, 50937, Cologne, Germany;4. University of Cologne, Faculty of Medicine and Cologne University Hospital, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Straße 62, 50937, Cologne, Germany;5. University of Cologne, Faculty of Medicine and Cologne University Hospital, Department of Nuclear Medicine, Kerpener Straße 62, 50937, Cologne, Germany;6. Max Planck Institute for Metabolism Research, Gleueler Straße 50, 50931, Cologne, Germany;1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China;2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China;3. Hefei YiGong Pharmaceutical Co. Ltd, Hefei 230088, China;1. Department of Radiology, School of Medicine, Washington University in Saint Louis, Saint Louis, MO 63110, United States;2. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;1. Department of Chemistry, Tsinghua University, Beijing 100084, PR China;2. The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China;3. Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, PR China;4. National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China;5. Bioinformatics and Drug Design Group, Department of Pharmacy, Centre for Computational Science and Engineering, National University of Singapore, 117543, Singapore |
| |
| 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. |
| |
| Keywords: | PARP-1 PET Radiolabeling Imaging |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
