In vitro and in vivo evaluation of [¹⁸F]ciprofloxacin for the imaging of bacterial infections with PET

The suitability of the ¹⁸F-labelled fluoroquinolone antibiotic ciprofloxacin ([¹⁸F]ciprofloxacin) for imaging of bacterial infections with positron emission tomography (PET) was assessed in vitro and in vivo.

For the in vitro experiments, suspensions of various E. coli strains were incubated with different concentrations of [¹⁸F]ciprofloxacin (0.01–5.0 μg/ml) and radioactivity retention was measured in a gamma counter. For the in vivo experiments, 725 ± 9 MBq [¹⁸F]ciprofloxacin was injected intravenously into four patients with microbiologically proven bacterial soft tissue infections of the lower extremities and time-radioactivity curves were recorded in infected and uninfected tissue for 5 h after tracer injection.

Binding of [¹⁸F]ciprofloxacin to bacterial cells was rapid, non-saturable and readily reversible. Moreover, bacterial binding of the agent was similar in ciprofloxacin-resistant and ciprofloxacin-susceptible clinical isolates. These findings suggest that non-specific binding rather than specific binding to bacterial type II topoisomerase enzymes is the predominant mechanism of bacterial retention of the radiotracer. PET studies in the four patients with microbiologically proven bacterial soft tissue infections demonstrated locally increased radioactivity uptake in infected tissue, with peak ratios between infected and uninfected tissue ranging from 1.8 to 5.5. Radioactivity was not retained in infected tissue and appeared to wash out with a similar elimination half-life as in uninfected tissue, suggesting that the kinetics of [¹⁸F]ciprofloxacin in infected tissue are governed by increased blood flow and vascular permeability due to local infection rather than by a binding process.

Taken together, our results indicate that [¹⁸F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET.