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

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-labelled radiotracers. Here, we report the radiochemical synthesis of [F]vinpocetine, fluorinated analogue of previously reported TSPO radioligand, [C]vinpocetine. Radiolabeling was achieved by [F]fluoroethylation of apovincaminic acid with [F]fluoroethyl bromide. [F]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 [F]vinpocetine as for [C]vinpocetine, including high blood-brain barrier permeability, regional uptake pattern and fast washout from the NHP brain. These results demonstrate that [F]fluorovinpocetine warrants further evaluation as an easier accessible alternative to [C]vinpocetine.