Exploring the potential of radiolabeled duramycin as an infection imaging probe

Abstract

AbstractThe continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60% PE. Therefore, duramycin is an attractive candidate for the formulation of probes for in situ visualization of E. coli driven focal infections. The aim of the present study is to develop 99mTc labeled duramycin as a single‐photon emission computed tomography (SPECT)‐based agent to image such infections. Duramycin was successfully conjugated with a bifunctional chelator, hydrazinonicotinamide (HYNIC). PE specificity of HYNIC‐duramycin was confirmed by a dye release assay on PE‐containing model membranes. Radiolabeling of HYNIC–duramycin with 99mTc was performed with consistently high radiochemical yield (>90%) and radiochemical purity (>90%). [99mTc]Tc‐HYNIC‐duramycin retained its specificity for E. coli, in vitro. SPECT and biodistribution studies showed that the tracer could specifically identify E. coli driven infection at 3 h post injection. While 99mTc‐labeled duramycin is employed for monitoring early response to cancer therapy and cardiotoxicity, the current studies have confirmed, for the first time, the potential of utilizing 99mTc labeled duramycin as an imaging agent for detecting bacteria. Its application in imaging PE‐positive bacteria represents a novel and promising advancement.