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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Majo, Vattoly J.¹  Arango, Victoria^1,2  Simpson, Norman R.²  Prabhakaran, Jaya¹  Kassir, Suham A.²  Underwood, Mark D.^1,2  Bakalian, Mihran²  Canoll, Peter³  Mann, J. John^1,2,4  Kumar, J. S. Dileep^1,2 

[1] Columbia Univ Coll Phys & Surg, Dept Psychiat, Div Mol Imaging & Neuropathol, New York, NY 10032 USA

[2] New York State Psychiat Inst & Hosp, New York, NY 10032 USA

[3] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA

[4] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA

关键词: IGF-1R;    Radiotracer;    PET;    Phosphor imaging;   

DOI  :  10.1016/j.bmcl.2013.05.026

来源: Elsevier

【 摘 要 】

Radiosynthesis and in vitro evaluation of [F-18](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 ([F-18]BMS-754807 or [F-18]1) a specific IGF-1R inhibitor was performed. [F-18]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 [F-18]TBAF in DMSO at 170 degrees C at high radiochemical purity and specific activity (1-2 Ci/mu mol, N = 10). The proof of concept of IGF-IR imaging with [F-18]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 [F-18]1 can be a potential PET tracer for monitoring IGF-1R. (C) 2013 Elsevier Ltd. All rights reserved.

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