Characterization and Reliability of [18F]2FNQ1P in Cynomolgus Monkeys as a PET Radiotracer for Serotonin 5-HT6 Receptors

摘要: Brain serotonin-6 receptor (5-HT6R) is the one of most recently identified serotonin receptors. Accumulating evidence suggests that it a potent therapeutic target for psychiatric and neurological diseases. Since [18F]2FNQ1P was proposed as first fluorinated PET radioligand this receptor, objective present study to demonstrate its suitability 5-HT6R neuroimaging in primates. characterized by vitro autoradiography vivo imaging cynomolgus monkeys. Following imaging, tracer binding indices were computed using simplified reference tissue model Logan graphical model, with cerebellum region. The reproducibility assessed test-retest five animals. Finally, specificity pre-injection antagonist, SB258585. In vitro, results showed wide cerebral distribution toward 5-HT6Rs effectively displaced brain penetration good reproducible at cortical subcortical levels. automated method gave best spatial normalization. indices, giving highest magnitude, lowest standard deviation robustness. antagonist significantly decreased mainly striatum sensorimotor cortex. Taken together, these preclinical show suitable reliable non-human primates encourage transfer humans.