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

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2270-2274. doi: 10.1016/j.bmcl.2019.06.037. Epub 2019 Jun 20.

Abstract

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.

Keywords: Fluorine-18; Kinetics; Monkey; PET; Radiometabolites; TSPO radioligands; Vinpocetine.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Fluorine Radioisotopes
  • Ligands
  • Macaca fascicularis
  • Models, Molecular
  • Molecular Structure
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, GABA / analysis*
  • Structure-Activity Relationship
  • Tissue Distribution
  • Vinca Alkaloids / chemical synthesis
  • Vinca Alkaloids / chemistry*
  • Vinca Alkaloids / pharmacokinetics

Substances

  • Fluorine Radioisotopes
  • Ligands
  • Radiopharmaceuticals
  • Receptors, GABA
  • TSPO protein, human
  • Vinca Alkaloids
  • vinpocetine