Quantification of 5-HT 1A receptors in human brain using p -MPPF kinetic modelling and PET

. Serotonin-1A (5-HT 1A ) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N -(2"-pyridinyl)- p -[ 18 F]fluorobenzamido] ethyl] piperazine ( p -MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT 1A receptors. To test p -MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p -MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p -MPPF and 5-HT 1A receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT 1A receptor brain distribution. In conclusion, our results show that p -MPPF is a suitable PET radioligand for 5-HT 1A receptor human studies.