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.
Sanabria-Bohórquez
Sandra M
SM
Present address: Merck Research Laboratories, 770 Sumneytown Pike, P.O. Box 4 WP44C-2, West Point, PA 19486, USA. sandra_sanabria@merck.com
Biver
Francoise
F
Damhaut
Philippe
P
Wikler
David
D
Veraart
Claude
C
Goldman
Serge
S
D000328:Adult; D000631:Aminopyridines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D008954:Models, Biological; D010879:Piperazines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000032:analysis*; D044263:Receptors, Serotonin, 5-HT1; D014055:Tomography, Emission-Computed
D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine