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. To better separate these etiologies, we recently developed positron emission tomography (PET) probes for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). In animal models and early human testing, these probes have shown great promise. Given the success of these initial probes, we wanted to expand the technology to include different radionuclides with longer half-lives (T½), as well as generator produced radionuclides. These new probes allow for imaging where there may be temporal limitations for optimal signal-to-noise ratios (S/N) at the target pathology, or for imaging where there is limited access to nuclear medicine techniques and infrastructure (such as PET/CT or cyclotrons). These new TMP derivatives are complimentary and broadly applicable bacterial infection monitoring reagents, which can be used for PET/CT or SPECT with either short-lived or long-lived radionuclides. These probes are able to enter bacteria, and most retain the ability to bind to their target, bacterial dihydrofolate reductase (eDHFR), with similar affinity to either trimethoprim or a similar molecule [18F]-FPTMP. Interestingly, some versions of the probes have markedly different minimum inhibitory concentration (MIC) values in E. Coli, suggesting that different probes could provide a better understanding of bacterial resistance mechanisms. The results of this work could significantly impact the diagnosis and monitoring of bacterial infections.

Translation from bench to bedside: Developing new infection-specific radiotracers

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.