Noninvasive pulmonary [18F]-2-fluoro-deoxy-D-glucose positron emission tomography correlates with bactericidal activity of tuberculosis drug treatment

Stephanie L. Davis, Eric Nuermberger, Peter K. Um, Camille Vidal, Bruno Jedynak, Martin Gilbert Pomper, William Ramses Bishai, Sanjay Jain

Research output: Contribution to journalArticle

Abstract

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 [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) was compared with standard microbiologic methods to monitor the response to treatment. [18F]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 [18F]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 costeffective studies of more expensive animal models of TB. Validated markers may also be useful as "point-ofcare" methods to monitor TB treatment in humans.

Original languageEnglish (US)
Pages (from-to)4879-4884
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number11
DOIs
StatePublished - Nov 2009

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Deoxyglucose
Positron-Emission Tomography
Tuberculosis
Lung
Pharmaceutical Preparations
Biomarkers
Aerosols
Mycobacterium tuberculosis
Animal Models
Technology
Recurrence

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

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abstract = "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 [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) was compared with standard microbiologic methods to monitor the response to treatment. [18F]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 [18F]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 costeffective studies of more expensive animal models of TB. Validated markers may also be useful as {"}point-ofcare{"} methods to monitor TB treatment in humans.",
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