1608477-84-4Relevant academic research and scientific papers
Preclinical validation of [18F]2FNQ1P as a specific PET radiotracer of 5-HT6 receptors in rat, pig, non-human primate and human brain tissue
Billard, Thierry,Bouvard, Sandrine,Courault, Pierre,Emery, Stéphane,Fieux, Sylvain,Iecker, Thibaut,Lancelot, Sophie,Tourvieille, Christian,Vidal, Benjamin,Zimmer, Luc
, p. 57 - 63 (2020/01/30)
Introduction: The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [18F]2FNQ1P, a new PET radiotracer of 5-HT6 receptors, in rat, pig, non-human primate and human tissues. The 5-HT6 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 [18F]2FNQ1P in cerebral regions with high 5-HT6 receptor density. Binding was blocked by addition of SB258585 as a specific antagonist. Binding assays provided KD and Bmax values of respectively 1.34 nM and 0.03 pmol·mg? 1 in rat, 0.60 nM and 0.04 pmol·mg? 1 in pig, 1.38 nM and 0.07 pmol·mg? 1 in non-human primate, and 1.39 nM and 0.15 pmol·mg? 1 in human caudate nucleus. In rat brain, the proportion of unmetabolized [18F]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 [18F]2FNQ1P is a specific radiotracer for molecular imaging of 5-HT6 receptors and suggest that it could be used as a radiopharmaceutical in humans.
Syntheses, radiolabelings, and in vitro evaluations of fluorinated pet radioligands of 5-HT6 serotoninergic receptors
Colomb, Julie,Becker, Guillaume,Fieux, Sylvain,Zimmer, Luc,Billard, Thierry
, p. 3884 - 3890 (2014/05/20)
The 5-HT6 receptors are potent therapeutic targets for psychiatric and neurological diseases (schizophrenia, Alzheimers disease, etc.). However, with lack of specific radiopharmaceuticals, their pharmacology is still incomplete and their exploration is limited to animal models. In this context, we have designed a fluorinated PET radiotracer, [18F]2FNQ1P, that possesses a high affinity and selectivity for 5-HT6. In vitro PET autoradiographies in rat brain sections with this radiotracer were in accordance with the 5-HT6 distribution pattern.
