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Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R

2013; Elsevier BV; Volume: 23; Issue: 14 Linguagem: Inglês

10.1016/j.bmcl.2013.05.026

1464-3405

Vattoly J. Majo, Victoria Arango, Norman R. Simpson, Jaya Prabhakaran, Suham Kassir, Mark D. Underwood, Mihran J. Bakalian, Peter Canoll, J. John Mann, J.S. Dileep Kumar,

Metabolism, Diabetes, and Cancer

Radiosynthesis and in vitro evaluation of [(18)F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([(18)F]BMS-754807 or [(18)F]1) a specific IGF-1R inhibitor was performed. [(18)F]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-dichloropyrrolo[2,1-f][1,2,4]triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [(18)F]TBAF in DMSO at 170°C at high radiochemical purity and specific activity (1-2Ci/μmol, N=10). The proof of concept of IGF-IR imaging with [(18)F]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 [(18)F]1 can be a potential PET tracer for monitoring IGF-1R.