Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumansIn Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates
Smart K, Zheng M, Holden D, Felchner Z, Zhang L, Han Y, Ropchan J, Carson R, Vasdev N, Huang Y. In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates. Pharmaceuticals 2023, 16: 194. PMID: 37259346, PMCID: PMC9959234, DOI: 10.3390/ph16020194.Peer-Reviewed Original ResearchPositron emission tomographyNon-human primatesMetabolite-corrected arterial input functionML/Free fractionWarrants further evaluationPotential therapeutic targetGood brain uptakeAdult rhesus macaquesPlasma free fractionArterial blood samplingGray matter regionsTwo-tissue compartment modelBrain uptakeRegional time-activity curvesBlood samplingPsychiatric disordersPET scansTherapeutic targetTime-activity curvesGray matterBrain regionsEmission tomographyFurther evaluationArterial input function