Various routes of administration of (99m)Tc-labeled synthetic lactoferrin antimicrobial peptide hLF 1-11 enables monitoring and effective killing of multidrug-resistant Staphylococcus aureus infections in mice

Peptides
C P J M Brouwer, M M Welling

Abstract

The synthetic antimicrobial peptide representative of the first 11 N-terminal amino acids of human lactoferrin (hLF 1-11) kills multidrug-resistant Staphylococcus aureus (MRSA). This study displays antimicrobial activity of hLF 1-11, via various routes of administration, against MRSA infections in mice. Radiolabeling hLF 1-11 with technetium-99m ((99m)Tc-hLF 1-11) enables scintigraphic monitoring directly after administration. (99m)Tc-hLF 1-11 was taken up by the gall bladder, intestines, and kidneys. Most of the radioactivity was captured in the urinary bladder and about 1% of the injected dose accumulated into infected thigh muscles. At 2 or 24h after either intravenously, subcutaneously, intraperitoneally, or orally injected a single dose of 0.04 mg/kg hLF 1-11 in mice significantly reduced (20-60 times) the number of viable MRSA. In a dose-response setting in immunocompetent mice maximum bactericidal effects (10,000 times reduction) of intravenously injected (99m)Tc-hLF 1-11 was seen with 40 mg/kg whereas the same dose of orally administered (99m)Tc-hLF 1-11 induced about approximately 100 times reduction. In conclusion, intravenously and orally administrated (99m)Tc-hLF 1-11 accumulates in infected tissues and is highly ef...Continue Reading

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Citations

Jul 1, 2008·Expert Opinion on Medical Diagnostics·Beth A Goins
Jun 15, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natascia BruniFranco Dosio
Jul 3, 2016·Fish & Shellfish Immunology·Claudio Andrés ÁlvarezLuis Mercado
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Oct 1, 2016·Pharmaceuticals·Francesco GiansantiGiovanni Antonini
Apr 1, 2020·Current Topics in Medicinal Chemistry·Andrea BossoElio Pizzo
Jul 16, 2019·Clinical Nuclear Medicine·Giulia Anna FollacchioMauro Liberatore

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