Artigo Acesso aberto Revisado por pares

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

2012; Elsevier BV; Volume: 22; Issue: 15 Linguagem: Inglês

10.1016/j.bmcl.2012.05.099

ISSN

1464-3405

Autores

Jaya Prabhakaran, Victoria Arango, Vattoly J. Majo, Norman R. Simpson, Suham Kassir, Mark D. Underwood, Hanish Polavarapu, Jeffrey N. Bruce, Peter Canoll, J. John Mann, J.S. Dileep Kumar,

Tópico(s)

Barrier Structure and Function Studies

Resumo

Synthesis and in vitro evaluation of [(18)F](R)-N-(4-bromo-2-fluorophenyl)-7-((1-(2-fluoroethyl)piperidin-3-yl)methoxy)-6-methoxyquinazolin-4-amine ((R)-[(18)F]FEPAQ or [(18)F]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. [(18)F]1 was synthesized by reaction of sodium salt of compound 2 with [(18)F]fluoroethyl tosylate in DMSO. The yield of [(18)F]1 was 20% (EOS based on [(18)F]F(-)) with >99% radiochemical purity and specific activity of 1-2 Ci/μmol (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 [(18)F]1 may be a promising radiotracer for imaging VEGFR2 in brain using PET.

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