MK-9470

MK-9470 is a selective, high-affinity, inverse agonist (human IC₅₀=0.7 nM) for the cannabinoid CB1 receptor (CB1R) developed for use in human brain imaging. IC50 & Target:IC50: 0.7 nM (Cannabinoid receptor)^[1] In Vitro: MK-9470 is a potent CB1R inverse agonist with 0.7 nM binding affinity for the human CB1R and a 60-fold selectivity for CB1R over CB2R. Extensive in vitro screening against >100 cerebral receptors/ion channels revealed no significant off-target activities. A total of six targets had affinities <5 μM, with the affinities ranging from 0.5 to 2.7 μM^[1]. In Vivo: [¹⁸F]MK-9470 is a very well behaved, CB1R-selective tracer in the rhesus monkey. Baseline PET scans shows rapid brain penetration and accumulation of [¹⁸F]MK-9470 in most gray matter regions of the brain as expected for binding to CB1R and consistent with autoradiography results. Uptake in white matter is significantly lower. In human, [¹⁸F]MK-9470 exhibits relatively slow brain kinetics reaching a plateau at about 120 min after bolus injection. Tracer uptake is observed in all gray matter regions and remained relatively constant from 120 to 360 min after tracer injection^[1]. After injection of [¹⁸F]MK-9470, all rats show concentrations of radioactivity in the brain in a pattern consistent with the known CB1 receptor distribution, i.e. the highest uptake in the cerebellum and caudate-putamen, and a good fairly uniform uptake in the cortex. [¹⁸F]MK9470 peak uptake values range from 0.6 to 1.6 SUV. [¹⁸F]MK-9470 uptake remains relatively constant from 300 min after tracer injection^[2].