Characterization in non-human primates of [18F]-2FNQ1P, a PET radiotracer for serotonin 5-HT6 receptors

492 Objectives Brain serotonin-6 receptor (5-HT6) is the one of the most recently identified serotonin receptors. 5-HT6 receptor is a potent therapeutic target for psychiatric and neurological diseases, e.g., schizophrenia, Alzheimer’s disease, and for obesity treatment. The objective of this study was to characterize in cynomolgus monkeys our recently developed 5-HT6 fluorine-18 labeled radioligand, [18F]-2FNQ1P. Methods The in vitro cerebral distribution of [18F]-2FNQ1P was evaluated by autoradiography in non-human primates, including competitions with serotonin or SB258585 (a 5-HT6 receptor antagonist). In vivo PET studies were also performed in six anaesthetized male cynomolgus monkeys to assess the reliability (test-retest protocol) and the specificity (antagonist pretreatment protocol) of [18F]-2FNQ1P binding. Results In vitro competition studies showed that the radioligand was displaced dose-dependently by the 5-HT6 antagonist SB258585 and by serotonin. PET scan data obtained with a high-resolution PET/CT camera revealed a good brain penetration and a reproducible binding at cortical and subcortical levels (orbitofrontal and cingulate cortices, thalamus and striatum). The pretreatment with the antagonist SB258585 decreased significantly the binding of [18F]-2FNQ1P, notably in the striatal region, revealing a good 5-HT6 receptor specificity of the radioligand. Finally, the non-linear method gave the better spatial normalization of [18F]-2FNQ1P binding when the Logan model displayed a more satisfying reliability. Conclusions All together, these results show that [18F]-2FNQ1P is the first fluorine-18 radiotracer suitable for 5-HT6 receptor imaging in non-human primates, encouraging its clinical development in nuclear medicine.