Evaluation of the Novel 5-HT4 Receptor PET Ligand [11C]SB207145 in the Göttingen Minipig

This study investigates 5-hydroxytryptamine 4 (5-HT4) receptor binding in the minipig brain with positron emission tomography (PET), tissue homogenate-binding assays, and autoradiography in vitro. The cerebral uptake and binding of the novel 5-HT4 receptor radioligand [11C]SB207145 in vivo was modelled and the outcome compared with postmortem receptor binding. Different models for quantification of [11C]SB207145 binding were evaluated: One-tissue and two-tissue compartment kinetic modelling, Logan arterial input, and three different reference tissue models. We report that the pig autoradiographic 5-HT4 receptor distribution resembles the human 5-HT4 receptor distribution with the highest binding in the striatum and no detectable binding in the cerebellum. We found that in the minipig brain [11C]SB207145 follows one-tissue compartment kinetics, and the simplified reference tissue model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for stria...