Synthesis of N4′-[18F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study

Syntheses and evaluation of fluoroalkylated ciprofloxacin analogues are described. Among these analogues, N-4'-3-fluoropropylciprofloxacin (16) showed the most efficient antibacterial activity against E. colt strains (DH5 alpha and TOP10) and a high binding affinity for DNA gyrase of bacteria. To develop bacteria-specific infection imaging agents for position emission tomography (PET), no-carrier-added N-4'-3-[F-18]fluoropropylciprofloxacin ([F-18]16) was prepared in two steps from N-4'-3-methanesufonyloxypropylciprofloxacin, resulting in a 40% radiochemical yield (decay corrected for 100 min) via the ten-alcohol media radiofluorination protocol with high radiochemical purity (>99%) as well as high specific activity (149 +/- 75 GBq/mu mol). The agent was stable (>90%), as shown by an in vitro human serum stability assay. A bacterial uptake and blocking study of [F-18]16 using authentic compound 16 in TOP10 cells demonstrated its high specific bacterial uptake. The results suggest that this radiotracer holds promise as a useful bacterial infection radiopharmaceutical for PET imaging.