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 differencesHumans
2021
Imaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699
Naganawa M, Nabulsi NB, Matuskey D, Henry S, Ropchan J, Lin SF, Gao H, Pracitto R, Labaree D, Zhang MR, Suhara T, Nishino I, Sabia H, Ozaki S, Huang Y, Carson RE. Imaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699. Journal Of Nuclear Medicine 2021, 63: 609-614. PMID: 34385336, DOI: 10.2967/jnumed.121.262430.Peer-Reviewed Original ResearchConceptsMultilinear analysis 1Test-retest variabilityPlasma concentrationsHealthy subjectsR occupancyR antagonistBrain regionsMetabolite-corrected arterial input functionAbsolute test-retest variabilityAdrenal axis activityNovel PET radiotracersSubstantial specific bindingDose-dependent fashionVasopressin 1b receptorTest-retest reproducibilityHalf maximal inhibitory concentrationAdverse eventsAxis activityOutcome measuresReceptor occupancyTime-activity curvesArginine vasopressinPosterior pituitaryDistribution volumeNeuropsychiatric disorders
2020
First-in-Human Assessment of 11C-LSN3172176, an M1 Muscarinic Acetylcholine Receptor PET Radiotracer
Naganawa M, Nabulsi N, Henry S, Matuskey D, Lin SF, Slieker L, Schwarz AJ, Kant N, Jesudason C, Ruley K, Navarro A, Gao H, Ropchan J, Labaree D, Carson RE, Huang Y. First-in-Human Assessment of 11C-LSN3172176, an M1 Muscarinic Acetylcholine Receptor PET Radiotracer. Journal Of Nuclear Medicine 2020, 62: 553-560. PMID: 32859711, PMCID: PMC8049371, DOI: 10.2967/jnumed.120.246967.Peer-Reviewed Original ResearchConceptsSimplified reference tissue modelM1 receptorsHealthy subjectsMuscarinic acetylcholine receptor subtype M1Distribution volumePET radiotracersAbsolute test-retest variabilityExcellent test-retest reproducibilityReference tissue model 2Total distribution volumeSuitable reference regionTest-retest reproducibilityTest-retest variabilityReference regionTest-retest protocolNondisplaceable distribution volumeReference tissue modelTest-retest studySubtypes M1Preclinical studiesRegional time-activity curvesAcetylcholine concentrationHuman studiesReceptor occupancyTime-activity curves
2017
Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches
Bhatt S, Hillmer AT, Nabulsi N, Matuskey D, Lim K, Lin S, Esterlis I, Carson RE, Huang Y, Cosgrove KP. Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches. Synapse 2017, 72 PMID: 29105121, PMCID: PMC6547815, DOI: 10.1002/syn.22016.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsPositron emission tomographyCorpus callosumAcetylcholine receptorsGreater receptor occupancyReference regionRegion-based quantificationMin bolusTobacco smokersFrontal cortexTobacco cigarettesReceptor occupancyConstant infusionDistribution volumeEmission tomographyCallosumSpecific bindingBrainReceptorsSmokersSmokingPutamenInfusionBolusCortexUse of Electronic Cigarettes Leads to Significant Beta2-Nicotinic Acetylcholine Receptor Occupancy: Evidence From a PET Imaging Study
Baldassarri SR, Hillmer AT, Anderson JM, Jatlow P, Nabulsi N, Labaree D, Cosgrove KP, O’Malley S, Eissenberg T, Krishnan-Sarin S, Esterlis I. Use of Electronic Cigarettes Leads to Significant Beta2-Nicotinic Acetylcholine Receptor Occupancy: Evidence From a PET Imaging Study. Nicotine & Tobacco Research 2017, 20: 425-433. PMID: 28460123, PMCID: PMC5896427, DOI: 10.1093/ntr/ntx091.Peer-Reviewed Original ResearchConceptsBlood nicotine levelsAlternative nicotine delivery systemsNicotinic acetylcholine receptorsElectronic cigarettesNicotine delivery systemsCigarette smokersCigarette smokingTobacco cigarettesReceptor occupancyAbuse liabilityAcetylcholine receptorsNicotine levelsEC challengeCigarette smoking groupPositron emission tomography studyTobacco cigarette smokingEmission tomography studiesPET imaging studiesSmoking groupNeurologic effectsNicotine challengeNicotine addictionNicotine usersNovel radiotracersImaging studies
2016
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
Girgis RR, Slifstein M, D’Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology 2016, 233: 3503-3512. PMID: 27525990, PMCID: PMC5035321, DOI: 10.1007/s00213-016-4382-y.Peer-Reviewed Original ResearchConceptsDopamine D3 receptorD2 receptorsD3 receptorsReceptor occupancyPartial agonistPositive symptomsD2 receptor partial agonistNegative symptomsPositron emission tomography scanDose-occupancy relationshipD2 receptor occupancyWeeks of dosingEmission tomography scanWeeks of treatmentExposure-response analysisReceptor partial agonistCerebrospinal fluid samplesDopamine D2 receptorsReward-related behaviorsD2 receptor ligandsTomography scanD2 antagonismPatientsDay 1Low dosesQuantitative projection of human brain penetration of the H3 antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy
Sawant-Basak A, Chen L, Shaffer CL, Palumbo D, Schmidt A, Tseng E, Spracklin DK, Gallezot JD, Labaree D, Nabulsi N, Huang Y, Carson RE, McCarthy T. Quantitative projection of human brain penetration of the H3 antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy. Xenobiotica 2016, 47: 119-126. PMID: 27353353, DOI: 10.3109/00498254.2016.1166531.Peer-Reviewed Original Research
2015
Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050
Naganawa M, Dickinson GL, Zheng MQ, Henry S, Vandenhende F, Witcher J, Bell R, Nabulsi N, Lin SF, Ropchan J, Neumeister A, Ranganathan M, Tauscher J, Huang Y, Carson RE. Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050. Journal Of Pharmacology And Experimental Therapeutics 2015, 356: 260-266. PMID: 26628406, PMCID: PMC4727157, DOI: 10.1124/jpet.115.229278.Peer-Reviewed Original ResearchConceptsHours postdosePositron emission tomographyReceptor occupancyEmission tomographySerious adverse eventsSingle oral dosesImportant therapeutic roleΚ-opioid receptorsSubstance abuse disordersFurther clinical testingHealthy human subjectsMultilinear analysis-1 (MA1) methodAntagonist radiotracersAdverse eventsOral dosesBrain penetrationTherapeutic rolePlasma concentrationsAbuse disordersEthanol consumptionLY2456302Clinical testingNovel radiotracersAlcohol dependenceDistribution volume
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 ResearchAssessing the sensitivity of [11C]p943, a novel 5‐HTIB radioligand, to endogenous serotonin release
Cosgrove KP, Kloczynski T, Nabulsi N, Weinzimmer D, Lin S, Staley JK, Bhagwagar Z, Carson RE. Assessing the sensitivity of [11C]p943, a novel 5‐HTIB radioligand, to endogenous serotonin release. Synapse 2011, 65: 1113-1117. PMID: 21484884, PMCID: PMC3149753, DOI: 10.1002/syn.20942.Peer-Reviewed Original ResearchConceptsFenfluramine-induced changesReceptor occupancyDoses of fenfluraminePositron emission tomography radioligandEndogenous serotonin releaseNonhuman primate brainSerotonin releaseLow doseHigh doseTomography radioligandPrimate brainRhesus monkeysFenfluramineRhesus macaquesPET imagingHuman brainBaboonsDoseDosesRadioligandBrainCurrent studyReceptors