In vivo quantification of 5-HT1A-[18F]MPPF interactions in rats using the YAP-(S)PET scanner and a beta-microprobe.
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.
Millet
Philippe
P
Psychiatric Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospital of Geneva, Switzerland. Philippe.Millet@sim.hcuge.ch <Philippe.Millet@sim.hcuge.ch>
Moulin
Marcelle
M
Bartoli
Antonietta
A
Del Guerra
Alberto
A
Ginovart
Nathalie
N
Lemoucheux
Laurent
L
Buono
Stephano
S
Fagret
Daniel
D
Charnay
Yves
Y
Ibáñez
Vicente
V
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
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin