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

Radiosynthesis and in vitro evaluation of [18F](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 ([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-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 [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.