HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nibbering, P. H. Articles by Pauwels, E. K.J. Search for Related Content PubMed PubMed Citation Articles by Nibbering, P. H. Articles by Pauwels, E. K.J.

^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

This article has been cited by other articles:

				A. M. van der Does, S. J. P. Bogaards, B. Ravensbergen, H. Beekhuizen, J. T. van Dissel, and P. H. Nibbering Antimicrobial Peptide hLF1-11 Directs Granulocyte-Macrophage Colony-Stimulating Factor-Driven Monocyte Differentiation toward Macrophages with Enhanced Recognition and Clearance of Pathogens Antimicrob. Agents Chemother., February 1, 2010; 54(2): 811 - 816. [Abstract] [Full Text] [PDF]

				D. Salber, J. Gunawan, K.-J. Langen, E. Fricke, P. Klauth, W. Burchert, and S. Zijlstra Comparison of 99mTc- and 18F-Ubiquicidin Autoradiography to Anti-Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses J. Nucl. Med., June 1, 2008; 49(6): 995 - 999. [Abstract] [Full Text] [PDF]

				M. Tulchinsky and A. M. Peters Leukocyte Receptor-Binding Radiopharmaceuticals for Infection and Inflammation Scintigraphy J. Nucl. Med., May 1, 2005; 46(5): 718 - 721. [Full Text] [PDF]

				M. S. Akhtar, A. Qaisar, J. Irfanullah, J. Iqbal, B. Khan, M. Jehangir, M. A. Nadeem, M. A. Khan, M. S. Afzal, I. ul-Haq, et al. Antimicrobial Peptide 99mTc-Ubiquicidin 29-41 as Human Infection-Imaging Agent: Clinical Trial J. Nucl. Med., April 1, 2005; 46(4): 567 - 573. [Abstract] [Full Text] [PDF]

				L. Dijkshoorn, C. P. J. M. Brouwer, S. J. P. Bogaards, A. Nemec, P. J. van den Broek, and P. H. Nibbering The Synthetic N-Terminal Peptide of Human Lactoferrin, hLF(1-11), Is Highly Effective against Experimental Infection Caused by Multidrug-Resistant Acinetobacter baumannii Antimicrob. Agents Chemother., December 1, 2004; 48(12): 4919 - 4921. [Abstract] [Full Text] [PDF]