Related Experiment Videos
99mTc-labeled antimicrobial peptides for detection of bacterial and Candida albicans infections
M M Welling1, A Lupetti, H S Balter
1Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Unlabelled:
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.
Insights
Technetium-99m-labeled antimicrobial peptides, such as ubiquicidin (UBI) and lactoferrin (hLF), show high accumulation in bacterial and fungal infections. These peptides effectively distinguish infected tissues from sterile inflammation, unlike ciprofloxacin.
Area of Science:
- Nuclear medicine
- Infectious disease imaging
- Antimicrobial peptide research
Background:
- Developing targeted imaging agents for infections is crucial.
- Antimicrobial peptides (AMPs) show selective binding to microorganisms.
- Synthetic AMPs derived from ubiquicidin (UBI) and lactoferrin (hLF) were investigated.
Purpose of the Study:
- To evaluate 99mTc-labeled UBI and hLF peptides for scintigraphic detection of infections.
- To compare peptide accumulation in infected vs. sterile inflammatory lesions.
- To assess the diagnostic potential of these novel radiotracers.
Main Methods:
- 99mTc-labeled UBI and hLF peptides, defensins, ciprofloxacin, and IgG were injected intravenously in mice and rabbits.
- Bacterial (Staphylococcus aureus, Klebsiella pneumoniae) and fungal (Candida albicans) infections were established.
- Sterile inflammation was induced using heat-killed microbes or lipopolysaccharide (LPS).
- Scintigraphy and tissue radioactivity counts were used to quantify accumulation up to 4 hours post-injection.
Main Results:
- 99mTc-labeled UBI peptides (UBI 29-41, UBI 18-35, UBI 31-38), hLF 1-11, and defensins showed significantly higher accumulation (P < 0.01) in infected tissues compared to sterile inflammation.
- These peptides demonstrated preferential accumulation in both bacterial and fungal infections.
- 99mTc-labeled ciprofloxacin did not show significant differences in accumulation between infected and sterile inflamed tissues.
Conclusions:
- 99mTc-labeled UBI and hLF peptides effectively accumulate in tissues infected with bacteria and Candida albicans.
- These peptides exhibit significantly lower accumulation in sterile inflammatory lesions, indicating high specificity.
- The findings suggest these radiolabeled peptides are promising agents for targeted scintigraphic detection of microbial infections.