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Microbial Targeting of ^99mTc-Labeled Recombinant Human β-Defensin-3 in an Animal Model of Infection: A Feasibility Pilot Study

¹ Nuclear Medicine Unit, Department of Radiological Sciences, "La Sapienza" Rome University, Rome, Italy; ² Perinatology and Puericulture Unit, Laboratory of Biochemistry of Sex Hormones, Department of Gynaecological Sciences, "La Sapienza" Rome University, Rome, Italy; ³ Department of Human Physiology and Pharmacology, "La Sapienza" Rome University, Rome, Italy; ⁴ Department of Experimental Medicine and Pathology, "La Sapienza" Rome University, Rome, Italy; ⁵ Nuclear Medicine Service, Department of Veteran Affairs Health System, Ann Arbor, Michigan; and ⁶ Department of Nuclear Medicine, "S. Maria della Misericordia" Hospital, Rovigo, Italy

Correspondence: For correspondence or reprints contact: Domenico Rubello, Department of Nuclear Medicine, PET Center, "S. Maria della Misericordia" Hospital, V. le Tre Martiri 140, 45100 Rovigo, Italy. E-mail: domenico.rubello{at}libero.it

Human β-defensin-3 (HBD-3) is an antimicrobial peptide with bactericidal effects on many gram-positive and gram-negative bacteria and some yeast species and, if radiolabeled, might be used to distinguish bacterial infection from sterile inflammation. The goals of the present study were to develop methods for radiolabeling HBD-3 with ^99mTc and to perform preliminary investigations on ^99mTc-labeled HBD-3 as a means to evaluate induced infection in an animal model. To this purpose, Staphylococcus aureus–induced infection was used to evaluate the capability of ^99mTc-HBD-3 to distinguish infection from aseptic inflammation in rats. Methods: Twenty to 40 µg of recombinant HBD-3 were labeled with ^99mTc⁺ hexa-coordinated with 3 molecules of CO and H₂O and separated by a column from free ^99mTc. ^99mTc-HBD-3 was added to cultures of a bacterial suspension of S. aureus and Escherichia coli to evaluate in vitro antibacterial activity. A bacterial suspension of S. aureus and a carrageenan solution were used to induce infection and sterile inflammation, respectively, in opposite thighs of 9 adult rats. Three separate experiments were performed on groups of 3 rats each. The animals received different doses of ^99mTc-HBD-3 injected through a cannula into the jugular vein. After sacrifice of the animals, tissue samples were obtained from sites of infection, inflammation, and control muscle (left foreleg) at 1, 3, and 5 h after ^99mTc-HBD-3 administration. Tissue samples were weighed and then counted in a well-counter. Simultaneously, 1 mL of a standard solution of ^99mTc-HBD-3 corresponding to each administered dose was counted. Results: ^99mTc-HBD-3 retained antibacterial activity. Radioactivity in tissue samples from the infected sites was significantly higher than that in samples of either induced inflammation or normal control muscle (ratio, 3:1) at 3 and 5 h after injection, whereas similar radioactivity counts were observed for tissue samples from aseptic inflammation sites and normal control muscle. Conclusion: In this investigation, ^99mTc-HBD-3 retained antibacterial activity and successfully distinguished infection from aseptic inflammation in adult rats.

Key Words: infection • inflammation • antimicrobial cationic peptides • peptide imaging • adult rats

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