2024
Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation
Grun M, Honhar P, Wang Y, Rossano S, Khang M, Suh H, Fowles K, Kliman H, Cavaliere A, Carson R, Marquez‐Nostra B, Saltzman W. Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation. Bioengineering & Translational Medicine 2024, 9 PMCID: PMC11561825, DOI: 10.1002/btm2.10661.Peer-Reviewed Original ResearchVaginal dosage formsBioadhesive nanoparticlesCynomolgus monkeysAnalysis of inflammatory biomarkersVaginal microbicidesVaginal canalMultiple dosesInflammatory biomarkersTherapeutic efficacyVaginal fluidSystemic circulationLong-term deliveryNoninvasive imagingClinical translationDosage formsNon-human primatesDelivery vehiclesMonkeysDeliveryVaginitisUterusMicrobicidesSafety evaluationBiodistributionDose
2023
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
2022
Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1
Smart K, Zheng MQ, Ahmed H, Fang H, Xu Y, Cai L, Holden D, Kapinos M, Haider A, Felchner Z, Ropchan JR, Tamagnan G, Innis RB, Pike VW, Ametamey SM, Huang Y, Carson RE. Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1. Cerebrovascular And Brain Metabolism Reviews 2022, 42: 1398-1409. PMID: 35209743, PMCID: PMC9274863, DOI: 10.1177/0271678x221084416.Peer-Reviewed Original ResearchConceptsNon-human primatesNMDA receptorsML/GluN2B-containing NMDA receptorsFree fractionRegional non-displaceable binding potentialsNon-displaceable binding potentialGood brain uptakeAdult rhesus macaquesBrain uptakeOne-tissue compartment modelTime-activity curvesNovel radiotracersGray matterNeuropsychiatric disordersSelective radiotracerDisplaceable bindingRhesus macaquesTissue distributionAcceptable profilePotential translationRadiotracerCerebellumFurther investigationReceptors
2011
P4‐253: Receptor occupancy of the 5‐HT6 receptor antagonist SAM‐760 in non‐human primates and healthy human volunteers
Comery T, Zasadny K, Morris E, Antinew J, Bell J, Billing B, Boyden T, Esterlis I, Huang Y, Kupiec J, Kuszpit K, Leil T, Nabulsi N, Planeta‐Wilson B, Plotka A, Skaddan M, Vandal G, Carson R, Katz E, McCarthy T. P4‐253: Receptor occupancy of the 5‐HT6 receptor antagonist SAM‐760 in non‐human primates and healthy human volunteers. Alzheimer's & Dementia 2011, 7: s794-s795. DOI: 10.1016/j.jalz.2011.05.2278.Peer-Reviewed Original ResearchP3‐431: Translational receptor occupancy for the 5‐HT4 partial agonist PF‐04995274 in rats, non‐human primates and healthy volunteers
Grimwood S, Drummond E, Zasadny K, Skaddan M, Brodney M, Coffman K, Nicholas T, Duvvuri S, Raunig D, Leurent C, Rowinski C, Park Y, Ogden A, Sawant A, Miller E, Rapp T, Wang Y, Planeta‐Wilson B, Ropchan J, Carson R, Morris E, Ding Y, Katz E. P3‐431: Translational receptor occupancy for the 5‐HT4 partial agonist PF‐04995274 in rats, non‐human primates and healthy volunteers. Alzheimer's & Dementia 2011, 7: s653-s653. DOI: 10.1016/j.jalz.2011.05.1875.Peer-Reviewed Original Research