title: In vivo quantification of 5-HT1A-[18F]MPPF interactions in rats using the YAP-(S)PET scanner and a beta-microprobe.
abstract: We performed full modeling analysis of 5-HT(1A)-[(18)F]MPPF interactions using the beta-microprobe (beta P) and a YAP-(S)PET scanner. Sixteen Wistar rats were used for beta P (n=5) and YAP-(S)PET (n=5) acquisitions and metabolite studies (n=6). Time-concentration curves were obtained in the hippocampus, raphe dorsalis, frontal cortex and cerebellum, using three injections of [(18)F]MPPF at different specific activities. B'(max) values were estimated from a two (2T-5k)- and three (3T-7k)-tissue-compartment model with beta P and YAP-(S)PET time-concentration curves. The simplified reference tissue model (SRTM) was used to estimate binding potential (BP(SRTM)) values from data obtained with the first injection and the cerebellum as the reference region. Overall, the 3T-7k model provided a better fit than the 2T-5k model, as evaluated from AIC criteria in all experiments. The rank order of receptor density (B'max) values was as follows: hippocampus>raphe approximately frontal cortex>cerebellum. Non-negligible specific binding was observed in the cerebellum (B'max (beta P)=1.5+/-0.9 pmol/ml). Significant correlations (p<0.001) between B'max and BP(SRTM) values were evident with both beta P (r=0.895) and YAP-(S)PET (r=0.695). The YAP-(S)PET system underestimated the [18F]MPPF binding levels in brain due to limited resolution (i.e. partial volume), but led to similar conclusions.
authors.affiliation: Psychiatric Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospital of Geneva, Switzerland. Philippe.Millet@sim.hcuge.ch <Philippe.Millet@sim.hcuge.ch>
authors.forename: Philippe
authors.initials: P
authors.lastname: Millet
authors.forename: Marcelle
authors.initials: M
authors.lastname: Moulin
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bartoli
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Guerra
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ginovart
authors.forename: Laurent
authors.initials: L
authors.lastname: Lemoucheux
authors.forename: Stephano
authors.initials: S
authors.lastname: Buono
authors.forename: Daniel
authors.initials: D
authors.lastname: Fagret
authors.forename: Yves
authors.initials: Y
authors.lastname: Charnay
authors.forename: Vicente
authors.initials: V
authors.lastname: Ibáñez
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin