Radiosynthesis and bioimaging of the tuberculosis chemotherapeutics isoniazid, rifampicin and pyrazinamide in baboons

J Med Chem. 2010 Apr 8;53(7):2882-91. doi: 10.1021/jm901858n.


The 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 [(11)C]CH(3)I to label RIF and [(11)C]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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / metabolism
  • Antitubercular Agents / pharmacokinetics*
  • Blood Proteins / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes / chemistry
  • Humans
  • Isoniazid / chemical synthesis
  • Isoniazid / chemistry
  • Isoniazid / metabolism
  • Isoniazid / pharmacokinetics
  • Papio / metabolism*
  • Positron-Emission Tomography*
  • Pyrazinamide / chemical synthesis
  • Pyrazinamide / chemistry
  • Pyrazinamide / metabolism
  • Pyrazinamide / pharmacokinetics
  • Rifampin / chemical synthesis
  • Rifampin / chemistry
  • Rifampin / metabolism
  • Rifampin / pharmacokinetics
  • Thorax / diagnostic imaging
  • Thorax / metabolism
  • Tissue Distribution


  • Antitubercular Agents
  • Blood Proteins
  • Carbon Radioisotopes
  • Pyrazinamide
  • Isoniazid
  • Rifampin