Novel Imaging Tracers for Rapid and Noninvasive Assessment of Bacterial Infections
Sanjay Jain1

1Johns Hopkins Medical Institute

Synopsis

We are developing novel imaging tracers for rapid and noninvasive assessment of bacterial infections and to study antimicrobial pharmacokinetics.

tuberculosis, infection, bacteria, PET, MRI, pharmacokinetics

Current tools to diagnose and monitor infections are dependent upon sampling suspected sites, and then performing culture or molecular techniques. This approach is invasive, often dangerous, time consuming, and is subject to incorrect sampling and contamination. Molecular imaging is a powerful, noninvasive tool that can rapidly provide three-dimensional views of disease processes deep within the body. Moreover, it has the fundamental advantage (with significant potential for clinical translation), to conduct noninvasive longitudinal assessments of the same patient. We have pioneered the development of molecular imaging specific for infectious diseases. Our overall goals are to develop novel imaging tracers for rapid and noninvasive assessment of bacterial infections and to study antimicrobial pharmacokinetics. These technologies are an emerging field of research, overcome several fundamental limitations of current tools, and will have a broad impact on both basic research and patient care. Beyond diagnosis and monitoring disease, these technologies will also provide a uniform cross-species platform for animal studies; allow unique insights into understanding disease pathogenesis; and expedite bench-to-bedside translation of new therapeutics. Finally, since molecular imaging is readily available for humans, validated tracers will become valuable tools for clinical applications, and for enabling personalized medicine for infectious diseases.

Acknowledgements

These studies were funded by the National Institutes of Health Director’s Transformative Research Award R01-EB-020539 (S.K.J.), NIH Director’s New Innovator Award DP2-OD-006492 (S.K.J.), and NIH R01-HL-116316 (S.K.J.).

References

1. Weinstein EA, Ordonez AA, DeMarco VP, Murawski AM, Pokkali S, MacDonald EM, Klunk M, Mease RC, Pomper MG, Jain SK. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography. Sci Transl Med. 2014 Oct 22; 6(259):259ra146. doi: 10.1126/scitranslmed.3009815. [Cover article].

2. Ordonez AA, Pokkali S, DeMarco VP, Klunk M, Mease RC, Foss CA, Pomper MG, Jain SK. Radioiodo-DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice. Antimicrob Agents Chemother. 2015 Jan;59(1):642-9. doi: 10.1128/AAC.04180-14.

3. DeMarco VP, Ordonez AA, Klunk M, Prideaux B, Wang H, Zhuo Z, Tonge PJ, Dannals RF, Holt DP, Lee CK, Weinstein EA, Dartois V, Dooley KE, Jain SK. Determination of 11C-Rifampin Pharmacokinetics within Mycobacterium tuberculosis-Infected Mice Using Dynamic Positron Emission Tomography Bioimaging. Antimicrob Agents Chemother. 2015 Sep;59(9):5768-74.

4. Salazar-Austin N, Ordonez AA, Hsu A, Benson JE, Mahesh M, Menachery E, Razeq JH, Salfinger M, Starke JR, Milstone AM, Parrish N, Nuermberger EL, Jain SK. Extensively Drug-Resistant Tuberculosis in a Young Child after Travel to India. Lancet Infect Dis. 2015;15:1485-91.

5. Xu J, DeMarco VP, Pokkali S, Ordonez AA, Klunk M, Penet MF, Bhujwalla Z, van Zijl PC, Jain SK. In situ pH effects within Mycobacterium tuberculosis Infected Mice revealed by UTE-CEST MRI. ISMRM. Toronto, Canada 2015.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)