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^99mTc-Labeled UBI 29-41 Peptide for Monitoring the Efficacy of Antibacterial Agents in Mice Infected with Staphylococcus aureus

¹ Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
² Division of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
³ AM-Pharma, Bunnik, The Netherlands
⁴ Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università degli Studi di Pisa, Pisa, Italy

Based on our earlier observation that ^99mTc-UBI 29-41, a radiolabeled peptide derived from ubiquicidin (UBI), discriminates between infections and sterile inflammatory processes, we considered the possibility that this tracer could be used for monitoring the efficacy of antibacterial agents in animals infected with Staphylococcus aureus. Methods: We injected ^99mTc-UBI 29-41 into S. aureus–infected mice after treatment with various doses of cloxacillin or erythromycin. At intervals thereafter, accumulation of the radiolabeled peptide at the site of infection was assessed by scintigraphy. When S. aureus was antibiotic resistant, we evaluated the efficacy of hLF 1-11, an antimicrobial peptide derived from human lactoferrin (hLF), in rats using ^99mTc-UBI 29-41 and scintigraphy. Results: Decreasing amounts of radiolabeled peptide at the site of the S. aureus infection in animals correlated (r² > 0.81; P < 0.001) with increasing doses of cloxacillin in animals. An effective dose of erythromycin resulted in reduced (P = 0.023) accumulation of the radiolabeled peptide at the site of S. aureus infection in mice. In addition, we noted decreasing amounts of ^99mTc-UBI 29-41 at the site of infection after administration of increasing doses of hLF 1-11 peptide in rats infected with antibiotic-resistant S. aureus. Furthermore, the number of viable bacteria decreased with increasing doses of cloxacillin or hLF 1-11 peptide, and a good correlation (r² > 0.80; P < 0.001) between the accumulation of ^99mTc-UBI 29-41 and the number of viable (antibiotic-resistant) S. aureus at the site of infection was seen. In an attempt to explain these results, we found that these antibacterial agents do not affect the in vitro binding of ^99mTc-UBI 29-41 to bacteria. Furthermore, this radiolabeled peptide bound to free bacteria and to cell-adherent but not phagocytized S. aureus, suggesting that at sites of infection mainly extracellular bacteria are targeted by ^99mTc-UBI 29-41. Conclusion: ^99mTc-UBI 29-41 allows the monitoring of the efficacy of antibacterial agents in mice and rats with S. aureus infections.

Key Words: antibiotics • infection • lactoferrin peptide • monitoring therapy • Staphylococcus aureus • ^99mTc labeling • ubiquicidin peptide

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