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

: Nag S, Krasikova R, Airaksinen AJ, Arakawa R, Petukhovd M, Gulyas B

Publisher: PERGAMON-ELSEVIER SCIENCE LTD

: 2019

: Bioorganic and Medicinal Chemistry Letters

: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

: BIOORG MED CHEM LETT

: 29

: 16

: 2270

: 2274

: 5

: 0960-894X

DOI: https://doi.org/10.1016/j.bmcl.2019.06.037

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 F-18-labelled radiotracers. Here, we report the radiochemical synthesis of [F-18]vinpocetine, fluorinated analogue of previously reported TSPO radioligand, [C-11]vinpocetine. Radiolabeling was achieved by [F-18]fluoroethylation of apovincaminic acid with [F-18]fluoroethyl bromide. [F-18]vinpocetine was obtained in quantities >2.7 GBq in RCY of 13% (non-decay corrected), and molar activity >60 GBq/mu mol within 95 min synthesis time. Preliminary PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [F-18]vinpocetine as for [C-11]vinpocetine, including high blood-brain barrier permeability, regional uptake pattern and fast washout from the NHP brain. These results demonstrate that [F-18]fluorovinpocetine warrants further evaluation as an easier accessible alternative to [C-11]vinpocetine.