Synthesis and biological evaluation of [18F]fluorovinpocetine, a potential PET radioligand for TSPO imaging

• Published in: Bioorganic & medicinal chemistry letters 2019-08, Vol.29 (16), p.2270-2274
• Main Authors: Nag, S., Krasikova, R., Airaksinen, A.J., Arakawa, R., Petukhovd, M., Gulyas, B.
• Format: Article
• Language: English
• Subjects: Fluorine-18; Kinetics; Medicin och hälsovetenskap; Monkey; PET; Radiometabolites; TSPO radioligands; Vinpocetine
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2019.06.037

Fluorine-18 labelled [18F]fluorovinpocetine, a potential PET radioligand for TSPO imaging. [Display omitted] Despite of various PET radioligands targeting the translocator protein TSPO 18-KDa are used for the investigations of neuroinflammatory conditions associated with neurological disorders, development of new TSPO radiotracers is still an active area of the researches with a major focus on the 18F-labelled radiotracers. Here, we report the radiochemical synthesis of [18F]vinpocetine, fluorinated analogue of previously reported TSPO radioligand, [11C]vinpocetine. Radiolabeling was achieved by [18F]fluoroethylation of apovincaminic acid with [18F]fluoroethyl bromide. [18F]vinpocetine was obtained in quantities >2.7 GBq in RCY of 13% (non–decay corrected), and molar activity >60 GBq/µmol within 95 min synthesis time. Preliminary PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [18F]vinpocetine as for [11C]vinpocetine, including high blood-brain barrier permeability, regional uptake pattern and fast washout from the NHP brain. These results demonstrate that [18F]fluorovinpocetine warrants further evaluation as an easier accessible alternative to [11C]vinpocetine.