期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 53, 期 11, 页码 4879-4884出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00789-09
关键词
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资金
- Bill & Melinda Gates Foundation TB Drug Accelerator [48793]
- NIH [AI079590, N01 AI30036, CA92871]
- Johns Hopkins Fund for Medical Discovery
- Potts Memorial Foundation
Tools for monitoring response to tuberculosis (TB) treatment are time-consuming and resource intensive. Noninvasive biomarkers have the potential to accelerate TB drug development, but to date, little progress has been made in utilizing imaging technologies. Therefore, in this study, we used noninvasive imaging to monitor response to TB treatment. BALB/c and C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered bactericidal (standard and highly active) or bacteriostatic TB drug regimens. Serial pulmonary [F-18]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) was compared with standard microbiologic methods to monitor the response to treatment. [F-18]FDG-PET correctly identified the bactericidal activity of the drug regimens. Imaging required fewer animals; was available in real time, as opposed to having CFU counts 4 weeks later; and could also detect TB relapse in a time frame similar to that of the standard method. Lesion-specific [F-18]FDG-PET activity also broadly correlated with TB treatment in C3HeB/FeJ mice that develop caseating lesions. These studies demonstrate the application of noninvasive imaging to monitor TB treatment response. By reducing animal numbers, these biomarkers will allow cost-effective studies of more expensive animal models of TB. Validated markers may also be useful as point-of-care methods to monitor TB treatment in humans.
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