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dc.contributor.authorLiu, Li
dc.contributor.authorXu, Youwen
dc.contributor.authorShea, Colleen
dc.contributor.authorFowler, Joanna S.
dc.contributor.authorHooker, Jacob M
dc.contributor.authorTonge, Peter J.
dc.date.accessioned2017-07-20T21:36:42Z
dc.date.issued2010
dc.identifier.citationLiu, Li, Youwen Xu, Colleen Shea, Joanna S. Fowler, Jacob M. Hooker, and Peter J. Tonge. 2010. “Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons.” Journal of Medicinal Chemistry 53 (7) (April 8): 2882–2891. doi:10.1021/jm901858n.en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33471161
dc.description.abstractThe front-line tuberculosis (TB) chemotherapeutics isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) have been labeled with carbon-11 and the biodistribution of each labeled drug has been determined in baboons using positron emission tomography (PET). Each radiosynthesis and formulation has been accomplished in 1 h, using [11C]CH3I to label RIF and [11C]HCN to label INH and PZA. Following iv administration, INH, PZA, RIF, and/or their radiolabeled metabolites clear rapidly from many tissues; however, INH, PZA, and/or their radiolabeled metabolites accumulate in the bladder while RIF and/or its radiolabeled metabolites accumulates in the liver and gall bladder, consistent with the known routes of excretion of the drugs. In addition, the biodistribution data demonstrate that the ability of the three drugs and their radiolabeled metabolites to cross the blood−brain barrier decreases in the order PZA > INH > RIF, although in all cases the estimated drug concentrations are greater than the minimum inhibitory concentration (MIC) values for inhibiting bacterial growth of Mycobacterium tuberculosis (MTB). The pharmacokinetic (PK) and drug distribution data have important implications for treatment of disseminated TB in the brain and pave the way for imaging the distribution of the pathogen in vivo.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofdoi:10.1021/jm901858nen_US
dash.licenseMETA_ONLY
dc.titleRadiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboonsen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalJournal of Medicinal Chemistryen_US
dash.depositing.authorHooker, Jacob M
dash.embargo.until10000-01-01
dc.identifier.doi10.1021/jm901858n*
workflow.legacycommentsosc.revisit MMen_US
dash.contributor.affiliatedHooker, Jacob


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