In vivo quantification of 5-HT 1A–[ 18F]MPPF interactions in rats using the YAP-(S)PET scanner and a β-microprobe

Abstract

We performed full modeling analysis of 5-HT 1A–[ 18F]MPPF interactions using the β-microprobe (βP) and a YAP-(S)PET scanner. Sixteen Wistar rats were used for βP ( 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 [ 18F]MPPF at different specific activities. B′ max values were estimated from a two (2T-5k)- and three (3T-7k)-tissue-compartment model with βP 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 ≈ frontal cortex > cerebellum. Non-negligible specific binding was observed in the cerebellum ( B′ max (βP) = 1.5 ± 0.9 pmol/ml). Significant correlations ( p < 0.001) between B′ max and BP SRTM values were evident with both βP ( 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.