Bacterial infection imaging with [18F]fluoropropyl-trimethoprim

Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8372-8377. doi: 10.1073/pnas.1703109114. Epub 2017 Jul 17.

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, 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. 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.

Keywords: PET; bacteria; imaging; radiotracer; trimethoprim.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • Escherichia coli / metabolism*
  • Escherichia coli Infections / diagnosis*
  • Escherichia coli Infections / microbiology
  • Fluorine Radioisotopes / chemistry
  • HCT116 Cells
  • Humans
  • Macaca mulatta
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Positron-Emission Tomography / methods*
  • Pseudomonas Infections / diagnosis*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / metabolism*
  • Radiopharmaceuticals / pharmacology
  • Staphylococcal Infections / diagnosis*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / metabolism*
  • Trimethoprim / chemistry
  • Trimethoprim / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Trimethoprim
  • Fluorine-18