Synthesis and in vitro evaluation of [18F](R)-FEPAQ: A potential PET ligand for VEGFR2

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Prabhakaran, Jaya¹  Arango, Victoria^1,2  Majo, Vattoly J.¹  Simpson, Norman R.^1,2  Kassir, Suham A.²  Underwood, Mark D.^1,2  Polavarapu, Hanish¹  Bruce, Jeffrey N.³  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, Dept Neurol, New York, NY USA

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

关键词: VEGFR2;    Radiotracer;    PET;    Glioma;    Bioimaging;   

DOI  :  10.1016/j.bmcl.2012.05.099

来源: Elsevier

【 摘 要 】

Synthesis and in vitro evaluation of [F-18](R)-N-(4-bromo-2-fluorophenyl)-7-((1-(2-fluoroethyl)piperidin-3-yl) methoxy)-6-methoxyquinazolin-4-amine ((R)-[F-18]FEPAQ or [F-18]1), a potential imaging agent for the VEGFR2, using phosphor image autoradiography are described. Synthesis of 2, the desfluoroethyl precursor for (R)-FEPAQ was achieved from t-butyl 3-(hydroxymethyl) piperidine-1-carboxylate (3) in five steps and in 50% yield. [F-18]1 was synthesized by reaction of sodium salt of compound 2 with [F-18]fluoroethyl tosylate in DMSO. The yield of [F-18]1 was 20% (EOS based on [F-18]F) with >99% radiochemical purity and specific activity of 1-2 Ci/mu mol (n = 10). The total synthesis time was 75 min. The radiotracer selectively labeled VEGFR2 in slide-mounted sections of human brain and higher binding was found in surgically removed human glioblastoma sections as demonstrated by in vitro phosphor imager studies. These findings suggest [F-18]1 may be a promising radiotracer for imaging VEGFR2 in brain using PET. (C) 2012 Elsevier Ltd. All rights reserved.

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