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^99mTc-Labeled Antimicrobial Peptides for Detection of Bacterial and Candida albicans Infections

Departments of Radiology and Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands; Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università degli Studi di Pisa, Pisa, Italy; and Centro de Investigaciones Nucleares and Cátedra de Radioquímica, Montevideo, Uruguay

This study compared the possibilities and limitations of ^99mTc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. The rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. ^99mTc-labeled human neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were included as control agents. Methods: ^99mTc-labeled peptides and control agents were injected intravenously into animals that had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscle. Up to 4 h after injection, the accumulation of ^99mTc-labeled compounds in the infected/inflamed thigh muscles was determined using scintigraphic techniques and radioactivity counts in dissected tissues. Results: Scintigraphy revealed that ^99mTc-labeled peptides UBI 29–41, UBI 18–35, UBI 31–38, hLF 1–11, and defensins, which showed preferential in vitro binding to microorganisms in a former study, accumulated at a significantly higher rate (P < 0.01) in bacterial and C. albicans infections in mice and rabbits than in inflamed tissues induced by heat-killed microorganisms or by LPS. No significant difference in the accumulation of ^99mTc-labeled ciprofloxacin was observed between infected and sterile inflamed thigh muscles in mice. Conclusion: ^99mTc-labeled antimicrobial peptides UBI 29–41, UBI 18–35, UBI 31–38, hLF 1–11, and defensins accumulate significantly in tissues infected with gram-positive and gram-negative bacteria and C. albicans. Significantly lower (P < 0.01) accumulation of these peptides occurs in sterile inflamed tissues. These data indicate that the peptides preferentially tag microorganisms at the site of infection, which is in agreement with their preferential binding to the microorganisms in vitro and in vivo. ^99mTc-labeled ciprofloxacin does not distinguish between infections and sterile inflammatory lesions, which implies that its specificity for the detection of bacterial infections is not warranted.

Key Words: antimicrobial peptides • ciprofloxacin • bacteria • Candida albicans • infection detection

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