The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [ 18 F]UCB-H was one first promising SV2A-ligands be labelled and used in vivo rodent human, while limited information on its pharmacokinetic properties available non-human primate. Here, we evaluate reliability three most commonly modelling approaches for cynomolgus primate, adding coupled fit non-displaceable distribution volume (V ND ) as an alternative approach improve unstable fit. The results are discussed light current state SV2A PET ligands. Results data optimally fitted with two-compartment model (2TCM), although did not always converge (large total T or large uncertainty estimate). 2TCM K 1 /k 2 across brain regions stabilized quantification, confirmed lower specific signal compared newest SV2A-ligands. However, measures V influx parameter (K similar what has been reported other These were reinforced by displacement studies using 19 F]UCB-H, demonstrating only 50% at maximal occupancy SV2A. As previously demonstrated clinical studies, graphical method Logan provided more robust estimate small bias 2TCM. Conclusions Modeling issues due slow component have ligands low binding, after blocking binding. all share chemical structural similarities, hypothesize that this binding common ligands, but hampers quantification when low.