title: The pharmacology of radiolabeled cationic antimicrobial peptides.
abstract: Cationic antimicrobial peptides are good candidates for new diagnostics and antimicrobial agents. They can rapidly kill a broad range of microbes and have additional activities that have impact on the quality and effectiveness of innate responses and inflammation. Furthermore, the challenge of bacterial resistance to conventional antibiotics and the unique mode of action of antimicrobial peptides have made such peptides promising candidates for the development of a new class of antibiotics. This review focuses on antimicrobial peptides as a topic for molecular imaging, infection detection, treatment monitoring and additionally, displaying microbicidal activities. A scintigraphic approach to studying the pharmacokinetics of antimicrobial peptides in laboratory animals has been developed. The peptides were labeled with technetium-99m and, after intravenous injection into laboratory animals, scintigraphy allowed real-time, whole body imaging and quantitative biodistribution studies of delivery of the peptides to the various body compartments. Antimicrobial peptides rapidly accumulated at sites of infection but not at sites of sterile inflammation, indicating that radiolabeled cationic antimicrobial peptides could be used for the detection of infected sites. As the number of viable micro-organisms determines the rate of accumulation of these peptides, radiolabeled antimicrobial peptides enabled to determine the efficacy of antibacterial therapy in animals to be monitored as well to quantify the delivery of antimicrobial peptides to the site of infection. The scintigraphic approach provides to be a reliable method for investigating the pharmacokinetics of small cationic antimicrobial peptides in animals and offers perspective for diagnosis of infections, monitoring antimicrobial therapy, and most important, alternative antimicrobial treatment infections with multi-drug resistant micro-organisms in humans.
authors.affiliation: AM-Pharma, Bunnik, The Netherlands.
authors.forename: Carlo P J M
authors.initials: CP
authors.lastname: Brouwer
authors.forename: Marty
authors.initials: M
authors.lastname: Wulferink
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics*; D054808:Histatins / Q000493:pharmacokinetics; D006801:Humans; D007553:Isotope Labeling; D007781:Lactoferrin / Q000502:physiology; D008969:Molecular Sequence Data; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012269:Ribosomal Proteins / Q000493:pharmacokinetics; D017556:Technetium Compounds / Q000493:pharmacokinetics