In Vitro Evidence for Competitive TSPO Binding of the Imaging Biomarker Candidates Vinpocetine and Two Iodinated DAA1106 Analogues in Post Mortem Autoradiography Experiments on Whole Hemisphere Human Brain Slices

Earlier in vivo PET experiments have demonstrated the binding of the neuroprotective alkaloid vinpocetine to the peripheral benzodiazepine receptor (PBR) or, with other terminology, the TSPO (18kDa translocator protein). With the aim of demonstrating the direct binding of vinpocetine to TSPO in vitro, two different ionidated versions of the novel TSPO ligand DAA1106 were used in autoradiographic experiments on human postmortem whole hemisphere brain slices. Vinpocetine effectively blocked the binding of both [I-125] desmethoxy-DAA1106 and [I-125] desfluoro-DAA1106 to TSPO, the decrease in binding reaching 30 % to 64 % in various brain structures. This present findings yield further evidence to vinpocetine's direct binding to the TSPO in the human brain in vitro as well as to the possible use of its radiolabelled versions as imaging biomarkers. The results also support the usefulness of two ionidated versions of DAA1106 as biomarkers of TSPO for in vitro and in vivo studies in neurological diseases accompanied with microglia activation.