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• W248226005 abstract "Isoniazid, also known as isonicotinylhydrazine (INH), is a first-line drug used in the prevention and treatment of tuberculosis (TB) (1, 2). INH is a prodrug that is activated by the catalase-peroxidase enzyme KatG of the mycobacteria. The activation process leads to the formation of the isonicotinic acyl-NADH complex. Subsequent binding of the complex with the enoyl-acyl carrier protein reductase InhA results in the inhibition of mycolic acid synthesis, which is essential for the wall of mycobacteria (3). INH is bactericidal to rapidly dividing mycobacteria but is bacteriostatic to slow-growing mycobacteria. INH labeled with 11C ([11C]INH) has been generated by Liu et al. for in vivo and real-time analysis of the INH pharmacokinetics (PK) and biodistribution with positron emission tomography (PET) (1). The half-life of 11C is 20.4 min, allowing for a ~60 min window to observe the PK.The PK and biodistribution of a novel drug are traditionally determined with blood and tissue sampling and/or autoradiography. Despite high workload and huge investment in drug development, only 8% of the drugs entering clinical trials today reach the market, as estimated by the U.S. Food and Drug Administration . One main reason for this attrition is insufficient exploration of the in vivo drug–target interaction (1). Traditional methods are inadequate to answer questions such as whether a drug reaches the target, how the drug interacts with its targets, and how the drug modifies the diseases. Because of the high resolution and sensitivity of newly developed imaging techniques, investigators have become increasingly interested in addressing these issues (4, 5). In the case of PET imaging, most small molecules can now be efficiently labeled with 11C or with 18F at >37 GBq/µmol (1 Ci/μmol), and they can be detected with PET in the nanomolar to picomolar concentration range (6-8). Consequently, a sufficient signal for imaging can be obtained even though the total amount of a radiotracer administered systemically is extremely low (known as microdosing, typically INH > RIF). The INH concentrations in the lungs and brain were ten times higher than the INH minimum inhibitory concentration (MIC) value against TB, supporting the use of INH for treating TB infections in the lungs and brain. This chapter summarizes the data obtained by Liu et al. regarding [11C]INH. The data obtained with regard to [11C]RIF and [11C]PZA are described in the MICAD chapters on [11C]RIF and [11C]PZA, respectively." @default.
• W248226005 created "2016-06-24" @default.
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• W248226005 date "2010-10-01" @default.
• W248226005 modified "2023-09-24" @default.
• W248226005 title "11C-Labeled isoniazid" @default.
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