Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases

Abstract

IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[18F] fluoro-D-glucose: [18F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.MethodsWe tested two specific radiotracers: 2-deoxy-2-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection.Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [18F]FDG in vitro. [18F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [18F]FPABA. Furthermore, [18F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.

Differentiation between responders and non-responders to antibiotic treatment in mice using 18F-Fluorodeoxysorbitol/PET

“…CDC estimates that at least 28% of antibiotics prescribed in the outpatient setting are unnecessary [15]. Therefore, it is critical to evaluate the effect of the timing of therapeutic intervention after infection and to get optimal treatment regimens in ensuring the prolonged effectiveness of these antibiotics [16,17]. When 250 CFU/mouse were used for infection, all mice developed lung infection with clear 18 F-FDS uptake within 2 days p.i.. No mice survived for more than 2 days p.i.…”

PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals

“…18 F-Fluorodeoxysorbitol ( 18 F-FDS) has already been tested in preclinical studies as an imaging probe with the capability to be enhanced in bacteria [101] and fungal diseases [102]; in healthy human volunteers, this tracer has shown no adverse reactions and the ability to specifically detect Enterobacteriaceae infections, showing suitability for human use from a radiation dosimetry perspective [103]. Unfortunately, no progress has been made in translating these results to routine human use.…”