Tc-99m-Labeled antimicrobial peptides for detection of bacterial and Candida albicans infections

This study compared the possibilities and limitations of Tc-99m-labeled syn thetic peptides derived from two human antimicrobial peptides, namely, ubiq uicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bac terial and fungal infections in mice and rabbits. The rationale of our appr oach was that selected peptides accumulate in infected areas but not in ste rile inflammatory lesions, because they bind preferentially to microorganis ms. Tc-99m-labeled human neutrophil peptides (defensins), ciprofloxacin, an d human polyclonal IgG were included as control agents. Methods: Tc-99m-lab eled peptides and control agents were injected intravenously into animals t hat had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Can dida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscl e. Up to 4 h after injection, the accumulation of Tc-99m-labeled compounds in the infected/inflamed thigh muscles was determined using scintigraphic t echniques and radioactivity counts in dissected tissues. Results: Scintigra phy revealed that Tc-99m-labeled peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins, which showed preferential in vitro binding to micr oorganisms in a former study, accumulated at a significantly higher rate (P < 0.01) in bacterial and C. albicans infections in mice and rabbits than i n inflamed tissues induced by heat-killed microorganisms or by LPS. No sign ificant difference in the accumulation of Tc-99m-labeled ciprofloxacin was observed between infected and sterile inflamed thigh muscles in mice. Concl usion: Tc-99m-labeled antimicrobial peptides UBI 29-41, UBI 18-35, UBI 31-3 8, hLF 1-11, and defensins accumulate significantly in tissues infected wit h gram-positive and gram-negative bacteria and C. albicans. Significantly l ower (P < 0.01) accumulation of these peptides occurs in sterile inflamed t issues. These data indicate that the peptides preferentially tag microorgan isms at the site of infection, which is in agreement with their preferentia l binding to the microorganisms in vitro and in vivo. Tc-99m-labeled ciprof loxacin does not distinguish between infections and sterile inflammatory le sions, which implies that its specificity for the detection of bacterial in fections is not warranted.