title: Synthesis and in vitro evaluation of [18F]BMS-754807: a potential PET ligand for IGF-1R.
abstract: 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.
authors.affiliation: Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, NY, USA.
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Suham A
authors.initials: SA
authors.lastname: Kassir
authors.forename: Mark D
authors.initials: MD
authors.lastname: Underwood
authors.forename: Mihran
authors.initials: M
authors.lastname: Bakalian
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: J
authors.initials: J
authors.lastname: John Mann
authors.forename: J S
authors.initials: JS
authors.lastname: Dileep Kumar
mesh_terms: D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008024:Ligands; D060787:Neoplasm Grading; D009369:Neoplasms / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D011859:Radiography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C545990:BMS 754807; D005462:Fluorine Radioisotopes; D008024:Ligands; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D014227:Triazines; D017526:Receptor, IGF Type 1