Synthesis and evaluation of Ciprofloxacin derivatives as diagnostic tools for bacterial infection by Staphylococcus aureus

Abstract

Development of target-specific diagnostic radiopharmaceuticals has always been a challenging task. For this purpose, design and development of the imaging-friendly variant of a potent antibiotic could aid in treatment planning and follow-up of patients with hard-to-diagnose bacterial infections. Fluoroquinolone analogues were synthesized taking the lead from Ciprofloxacin (the broad spectrum antibiotic) molecule. The idea of modifying fluoroquinolones, and subsequently labeling them, was to preserve their capacity to bind bacteria and thereby enable the compound to specifically target those microorganisms. Three compounds were thus synthesized as derivatives of Ciprofloxacin. The fluoroquinolone analogues were labeled with (99m)Tc by using (99m)Tc pertechnetate with high labeling efficiency for all the formulations. The complexes formed by chelation of (99m)Tc with our synthesized fluoroquinolone analogues showed good in vitro serum stability. The blood clearance study performed in New Zealand White rabbits exhibited a curve indicating the initial fast phase in which radiocomplexed drugs cleared from blood very quickly followed by a slow phase. The in vivo evaluation showed that fluoroquinolone-based radiopharmaceuticals bind to the bacteria present at the site of infection, which results in the retention of the agent at sites of active bacterial infection. The biodistribution data and the scintigrams demonstrated that Staphylococcus aureus bacteria in animal infection models took up the radiopharmaceutical formulations, confirming our hypothesis that (99m)Tc fluoroquinolone derivatives might be useful as diagnostic agents for targeted delivery in bacterial infections.