Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R |
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| Authors: | Vattoly J Majo Victoria Arango Norman R Simpson Jaya Prabhakaran Suham A Kassir Mark D Underwood Mihran Bakalian Peter Canoll J John Mann JS Dileep Kumar |
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| Institution: | 1. Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, NY, USA;2. New York State Psychiatric Institute, NY, USA;3. Department of Pathology, College of Physicians and Surgeons, NY, USA;4. Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA |
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| Abstract: | Radiosynthesis and in vitro evaluation of 18F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo2,1-f]1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide (18F]BMS-754807 or 18F]1) a specific IGF-1R inhibitor was performed. 18F]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo2,1-f]1,2,4]triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with 18F]TBAF in DMSO at 170 °C at high radiochemical purity and specific activity (1–2 Ci/μmol, N = 10). The proof of concept of IGF-IR imaging with 18F]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that 18F]1 can be a potential PET tracer for monitoring IGF-1R. |
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| Keywords: | IGF-1R Radiotracer PET Phosphor imaging |
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