This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Davis, S. L.
Right arrow Articles by Jain, S. K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davis, S. L.
Right arrow Articles by Jain, S. K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2009, p. 4879-4884, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00789-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Noninvasive Pulmonary [18F]-2-Fluoro-Deoxy-D-Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment{triangledown} ,{dagger}

Stephanie L. Davis,1,2 Eric L. Nuermberger,1,3 Peter K. Um,1,2 Camille Vidal,5,7 Bruno Jedynak,6,7 Martin G. Pomper,4 William R. Bishai,1,3 and Sanjay K. Jain1,2*

Center for Tuberculosis Research,1 Department of Pediatrics,2 Department of Medicine,3 Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287,4 Department of Biomedical Engineering,5 Department of Applied Mathematics and Statistics,6 Center for Imaging Science, Johns Hopkins University, Baltimore, Maryland 212187

Received 12 June 2009/ Returned for modification 15 July 2009/ Accepted 26 August 2009

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 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.

* Corresponding author. Mailing address: Center for Tuberculosis Research, 1550 Orleans Street, CRB-II, Rm 109, Baltimore, MD 21287. Phone: (410) 502-8241. Fax: (410) 614-8173. E-mail: sjain5{at}jhmi.edu

{triangledown} Published ahead of print on 8 September 2009.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4879-4884, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00789-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»