Imaging bacteria with radiolabelled quinolones, cephalosporins and siderophores for imaging infection: a systematic review

Abstract

Bacterial infections are still one of the main causes of patient morbidity and mortality worldwide. Nowadays, many imaging techniques, like computed tomography or magnetic resonance imaging, are used to identify inflammatory processes, but, although they recognize anatomical modifications, they cannot easily distinguish bacterial infective foci from non bacterial infections. In nuclear medicine, many efforts have been made to develop specific radiopharmaceuticals to discriminate infection from sterile inflammation. Several compounds (antimicrobial peptides, leukocytes, cytokines, antibiotics…) have been radiolabelled and tested in vitro and in vivo, but none proved to be highly specific for bacteria. Indeed factors, including the number and strain of bacteria, the infection site, and the host condition may affect the specificity of tested radiopharmaceuticals. Ciprofloxacin has been proposed and intensively studied because of its easy radiolabelling method, broad spectrum, and low cost, but at the same time it presents some problems such as low stability or the risk of antibiotic resistance. Therefore, in the present review studies with ciprofloxacin and other radiolabelled antibiotics as possible substitutes of ciprofloxacin are reported. Among them we can distinguish different classes, such as cephalosporins, fluoroquinolones, inhibitors of nucleic acid synthesis, inhibitors of bacterial cell wall synthesis and inhibitors of protein synthesis; then also others, like siderophores or maltodextrin-based probes, have been discussed as bacterial infection imaging agents. A systematic analysis was performed to report the main characteristics and differences of each antibiotic to provide an overview about the state of the art of imaging infection with radiolabelled antibiotics.

Siderophores for molecular imaging applications

“…These probes target predominantly secondary effects of infection such as increased blood flow and vascular permeability, activated endothelial cells or polymorphonuclear cell migration limiting their specificity or have other shortcomings related to blood manipulation or induction of immune response (HAMA) [29,30]. Even though new developments are emerging especially for bacterial infections such as radiolabelled antimicrobial peptides [26], nuclear medicine clinicians are still awaiting improved radiopharmaceuticals overcoming these limitations.…”

Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design

“…New diagnostic means should ideally specifically target bacteria (subspecies) and allow for their localization in the whole body of patients suffering from infections. In this respect, molecular imaging strategies based on labeled bacteria‐specific tracer molecules have been already proposed and preclinically tested; however, clinical translation is grossly lacking . Targeting bacteria for molecular imaging (or therapy) is especially challenging because many bacteria produce dense, impenetrable biofilms that limit access of tracer molecules to bacterial colonies.…”

Fluoroquinolones as imaging agents for bacterial infection

“…3 Although head-to-head comparisons have not been reported, compound 6 ( 99m Tc-labeled sitafloxacin) may be better at imaging S. aureus. 22, 48 Independent confirmation of sitafloxacin work would encourage comparisons with the thousands of other quinolones that are available for optimizing the quinolone moiety of the imaging agent (note that the agents need not be good therapeutics to be good diagnostics).…”

“…Consequently, work on 99m Tc-fluoroquinolone-based imaging is continuing. 3 To help focus efforts at quinolone refinement, we review why 99m Tc-ciprofloxacin has been considered a viable imaging agent, consider aspects of imaging that lack an adequate knowledge base, and suggest ways to move forward.…”