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Review

99mTc-Human β-defensin-3

Kam Leung  1
In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004.
[updated ].
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Review

99mTc-Human β-defensin-3

Kam Leung.
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Excerpt

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi (1). The mammalian defensins can be subdivided into three main classes according to their structural differences: α-defensins, β-defensins, and theta-defensins. Mammalian α-defensins are predominantly found in neutrophils and in small intestinal epithelial cells, whereas mammalian β-defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human β-defensins (human β-defensin-3 (HBD-3) and human β-defensin-4 (HBD-4)) have been identified. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity toward the Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Escherichia coli) and yeasts. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues such as leukocytes, heart, and skeletal muscle. HBD-4 is expressed in certain epithelial cells and in neutrophils.

A variety of radiolabeled compounds, including 67Ga-citrate, 99mTc-ciprofloxacin, 18F-FDG, and 111In- or 99mTc-labeled antibodies that interact with specific receptors on the infiltrating leukocytes, and peptides have been evaluated for the detection of infections (2, 3). However, because they accumulate in both infected and inflamed areas of the body, these radiopharmaceuticals are nonspecific and cannot distinguish between infection and inflammation. In an effort to identify and develop radioactive compounds that are specific for the detection of infections, various investigators have evaluated the use of antimicrobial peptides that are found naturally in most multicellular organisms (4). Such peptides bind specifically to microbes, presumably through cationic domains that interact with anionic regions of the microbial membrane, and have been shown to distinguish infected tissue from inflamed tissue (5). Liberatore et al. (6) radiolabeled HBD-3 with 99mTc for single-photon emission computed tomography imaging of infected tissue.

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