Non-invasive imaging is a powerful clinical tool for the early diagnosis, and monitoring of various disease processes. Next generation molecular imaging promises unparalleled opportunities for visualizing infections since molecular and cellular alterations occur earlier in a pathologic process, than structural changes. This rapidly developing technology has already become an essential tool in the field of oncology, with similar potential for infectious diseases. Differentiation of microbes by selective growth media, utilizin small molecules, is a mainstay of clinical microbiology. However, current tools to diagnose and monitor infections are dependent upon sampling suspected sites, and then performing culture or molecular techniques. This approach has several limitations - invasive, often dangerous, time consuming, and subject to incorrect sampling and contamination. We have exploited the unique biochemical pathways present within bacteria to develop a pipeline of novel and specific imaging tracers for detecting, quantifying and monitoring bacterial infections. As proof of concept, we systematically screened a library of 400 random 14C and 3H labeled compounds for metabolism and uptake by bacteria (but not host cells). From this library, we subsequently developed imaging tracers that could differentiate bacterial infections from non-infectious processes, and also allow discrimination between bacterial classes. Our central hypothesis is that small molecules metabolized by prokaryotic-specific pathways (but not host cells), could be developed into bacteria-specific imaging tracers that could differentiate infections from non-infectious processes and also provide information on the bacterial class causing the infection. We propose a multi-disciplinary collaboration, for developing a pipeline of novel imaging tracers for rapid and noninvasive assessment of bacterial infections that will provide a comprehensive platform to detect and discriminate a wide spectrum of pathogenic bacteria. In addition, we also propose the development of imaging as a platform to study multi-compartment pharmacokinetics of antimicrobial drugs. 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.

Public Health Relevance

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 to both basic research and patient care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB020539-01
Application #
8752061
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Sastre, Antonio
Project Start
2014-09-25
Project End
2019-05-31
Budget Start
2014-09-25
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$716,727
Indirect Cost
$274,303
Name
Johns Hopkins University
Department
None
Type
Other Domestic Higher Education
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218