Preclinical validation of [F]2FNQ1P as a specific PET radiotracer of 5-HT receptors in rat, pig, non-human primate and human brain tissue.

INTRODUCTION

The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [F]2FNQ1P, a new PET radiotracer of 5-HT receptors, in rat, pig, non-human primate and human tissues. The 5-HT receptor is one of the more recently identified serotonin receptors in central nervous system and, because of its role in memory and cognitive processes, is considered as a promising therapeutic target.

METHODS

In-vitro autoradiography and saturation binding assays were performed in postmortem brain tissues from rat, pig, non-human primate and human caudate nucleus, completed by serum stability assessment in all species and cerebral radiometabolite and biodistribution studies in rat.

RESULTS

In all species, autoradiography data revealed high binding levels of [F]2FNQ1P in cerebral regions with high 5-HT receptor density. Binding was blocked by addition of SB258585 as a specific antagonist. Binding assays provided K and B values of respectively 1.34 nM and 0.03 pmol·mg in rat, 0.60 nM and 0.04 pmol·mg in pig, 1.38 nM and 0.07 pmol·mg in non-human primate, and 1.39 nM and 0.15 pmol·mg in human caudate nucleus. In rat brain, the proportion of unmetabolized [F]2FNQ1P was >99% 5 min after iv injection and 89% at 40 min. The biodistribution studies found maximal radioactivity in lungs and kidneys (3.5 ± 1.2% ID/g and 2.0 ± 0.7% ID/g, respectively, 15 min post-injection).

CONCLUSION

These radiopharmacological data confirm that [F]2FNQ1P is a specific radiotracer for molecular imaging of 5-HT receptors and suggest that it could be used as a radiopharmaceutical in humans.