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Title: Bacterial infection imaging with [ 18F]fluoropropyl-trimethoprim

Abstract

There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here in this paper, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [ 18F]fluoropropyl-trimethoprim, or [ 18F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [ 18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [ 18F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. In conclusion, these results suggest that [ 18F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential.

Authors:
ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of Pennsylvania, Philadelphia, PA (United States). Department of Radiology
Publication Date:
Research Org.:
Trustees of the University of Pennsylvania, Philadelphia, PA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1371604
Alternate Identifier(s):
OSTI ID: 1465942
Grant/Contract Number:  
SC0012476; SE0012476
Resource Type:
Journal Article: Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 31; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
47 OTHER INSTRUMENTATION; 59 BASIC BIOLOGICAL SCIENCES; bacteria; imaging; PET; trimethoprim; radiotracer

Citation Formats

Sellmyer, Mark A., Lee, Iljung, Hou, Catherine, Weng, Chi-Chang, Li, Shihong, Lieberman, Brian P., Zeng, Chenbo, Mankoff, David A., and Mach, Robert H. Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. United States: N. p., 2017. Web. doi:10.1073/pnas.1703109114.
Sellmyer, Mark A., Lee, Iljung, Hou, Catherine, Weng, Chi-Chang, Li, Shihong, Lieberman, Brian P., Zeng, Chenbo, Mankoff, David A., & Mach, Robert H. Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. United States. doi:10.1073/pnas.1703109114.
Sellmyer, Mark A., Lee, Iljung, Hou, Catherine, Weng, Chi-Chang, Li, Shihong, Lieberman, Brian P., Zeng, Chenbo, Mankoff, David A., and Mach, Robert H. Mon . "Bacterial infection imaging with [18F]fluoropropyl-trimethoprim". United States. doi:10.1073/pnas.1703109114.
@article{osti_1371604,
title = {Bacterial infection imaging with [18F]fluoropropyl-trimethoprim},
author = {Sellmyer, Mark A. and Lee, Iljung and Hou, Catherine and Weng, Chi-Chang and Li, Shihong and Lieberman, Brian P. and Zeng, Chenbo and Mankoff, David A. and Mach, Robert H.},
abstractNote = {There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here in this paper, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [18F]fluoropropyl-trimethoprim, or [18F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [18F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. In conclusion, these results suggest that [18F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential.},
doi = {10.1073/pnas.1703109114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 31,
volume = 114,
place = {United States},
year = {Mon Jul 17 00:00:00 EDT 2017},
month = {Mon Jul 17 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1073/pnas.1703109114

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Cited by: 5 works
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