Design, synthesis and preliminary evaluation of 18F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Saccomanni, Giuseppe¹  Pascali, Giancarlo^2,3  Del Carlo, Sara¹  Panetta, Daniele²  De Simone, Mariarosaria²  Bertini, Simone¹  Burchielli, Silvia⁴  Digiacomo, Maria¹  Macchia, Marco¹  Manera, Clementina¹  Salvadori, Piero A.² 

[1] Univ Pisa, Dipartimento Farm, I-56126 Pisa, Italy

[2] CNR, Ist Fisiol Clin, I-56124 Pisa, Italy

[3] ANSTO LifeSci, Camperdown, NSW 2050, Australia

[4] Fdn Toscana G Monasterio, I-56124 Pisa, Italy

关键词: Cannabinoid;    CB2 receptor;    Iodonium derivatives;    Radiofluorination;    Microfluidic system;   

DOI  :  10.1016/j.bmcl.2015.04.055

来源: Elsevier

【 摘 要 】

In the present work, we report the synthesis of new aryliodonium salts used as precursors of single-stage nucleophilic F-18 radiofluorination. The corresponding unlabelled fluorinated derivatives showed to be CB2 cannabinoid receptor specific ligands, with K-i values in the low nanomolar range and high CB2/CB1 selectivity. The radiolabelled compound [F-18] CB91, was successfully formulated for in vivo administration, and its preliminary biodistribution was assessed with microPET/CT. This tracer presented a reasonable in vivo stability and a preferential extraction in the tissues that constitutionally express CB2 cannabinoid receptor. The results obtained indicate [18F] CB91 as a possible candidate marker of CB2 cannabinoid receptor distribution. This study would open the way to further validation of this tracer for assessing pathologies for which the expression of this receptor is modified. (C) 2015 Published by Elsevier Ltd.

【 授权许可】

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