Trends in Biotechnology
Radiopharmaceuticals: new antimicrobial agents
Section snippets
Large-scale production of antimicrobial peptides
Large quantities of purified microbial peptides are required to investigate their possible applications further. Difficulties arising in purifying natural antimicrobial peptides from various sources have prompted the recombinant production of antimicrobial peptides by genetically engineered bacteria 19, 20 or by peptide synthesis 21, 22. Such methods result in sufficient amounts of antimicrobial peptides produced under good laboratory practice conditions, which is essential for future approval
Measuring the pharmacokinetics of antimicrobial peptides
The classic method for studying the pharmacokinetics of small peptides in animals is to measure their levels in different organs at various intervals after injection using biochemical (or immunological) assays. A major disadvantage of this approach is that it does not allow whole-body, real-time monitoring of the biodistribution of the peptide in an individual animal. To circumvent this drawback, peptides need to be labelled to assess the biodistribution of the labelled peptides in animals. In
Radiolabelling of peptides
The aim of radiolabelling techniques is to firmly attach or incorporate the radionuclide into the peptide without altering its biological functions, thus allowing a reliable evaluation of its pharmacokinetics after intravenous administration. The various methods of labelling peptides with 99mTc, including indirect labelling using the preformed chelate approach or bifunctional chelating agents, and the direct labelling method have been discussed extensively 25, 26. The direct labelling method is
Application of labelled peptides for infection detection
Scintigraphic studies after intravenous injection of non-microbicidal concentrations of radiolabelled antimicrobial peptides into animals revealed that the peptides are rapidly cleared from the circulation (half-life 30–60 min) via the kidneys and bladder with little activity in the liver and no deposits in the intestines. Moreover, this favourable kinetic profile is accompanied by a limited radiation burden. An example of the scintigraphic data obtained with a 99mTc-labelled synthetic peptide
Outlook
Scintigraphic analysis of 99mTc-labelled peptides after intravenous injection is the method of choice for studying the pharmacokinetics of small antimicrobial peptides in animals because it allows reliable real-time, whole-body imaging and quantitative biodistribution studies without the need to kill animals at each interval. Using this approach, quantitative data can be obtained within seconds after injection of the radiolabelled peptide up to ∼12 h and the labelling procedure does not alter
References (35)
Antimycobacterial agent based on mRNA encoding human β-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis
Infect. Immun.
(2001)Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1
Proc. Natl Acad. Sci. U.S.A.
(2002)Chemical synthesis of β-defensins and LEAP-1/hepcidin
J. Pept. Res.
(2002)Complexes of technetium-99m with tetrapeptides containing one alanyl and three glycyl moieties
Eur. J. Nucl. Med.
(1996)Evaluation of 99mTc-ciprofloxacin scintigraphy in a rabbit model of Staphylococcus aureus prosthetic joint infection
J. Nucl. Med.
(2002)β-Defensin 1 contributes to pulmonary innate immunity in mice
Infect. Immun.
(2002)Cationic peptides: effectors in innate immunity and novel antimicrobials
Lancet Infect. Dis.
(2001)Antimicrobial peptides of multicellular organisms
Nature
(2002)- et al.
Defensins of vertebrate animals
Curr. Opin. Immunol.
(2002) Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation
J. Clin. Invest.
(1998)
Activity of novispirin G10 against Pseudomonas aeruginosa in vitro and in infected burns
Antimicrob. Agents Chemother.
In vitro activity of PR-39, a proline-arginine-rich peptide, against susceptible and multi-drug-resistant Mycobacterium tuberculosis
J. Antimicrob. Chemother.
Candidacidal activities of human lactoferrin peptides derived from the N terminus
Antimicrob. Agents Chemother.
Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria
Infect. Immun.
Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis
Antimicrob. Agents Chemother.
Synergistic and additive killing by antimicrobial factors found in human airway surface liquid
Am. J. Physiol. Lung Cell. Mol. Physiol.
Direct and indirect bacterial killing functions of neutrophil defensins in lung explants
Am. J. Physiol. Lung Cell. Mol. Physiol.
Cited by (48)
Radiolabeling and evaluation of a novel [<sup>99m</sup>TcN]<sup>2+</sup> complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging
2021, Bioorganic and Medicinal Chemistry LettersWater soluble and efficient amino acid Schiff base receptor for reversible fluorescence turn-on detection of Zn<sup>2+</sup> ions: Quantum chemical calculations and detection of bacteria
2016, Spectrochimica Acta - Part A: Molecular and Biomolecular SpectroscopyCitation Excerpt :In literature only very few articles report bacterial targeting probes for imaging. The bacteria targeting group employed were antibodies [38], lectins [39], sugars [40], antibiotic drugs [41], and peptides [42]. In the present investigation, we have employed a small organic molecule (Schiff base), as a probe for sensing bacterial cell membranes.
Potential role of antimicrobial peptides in the early onset of Alzheimer's disease
2015, Alzheimer's and DementiaCitation Excerpt :Tracers that can diagnose specific infectious processes and monitor effectiveness of (antimicrobial or anti-inflammatory) therapy are therefore of great promise. During the last decade, various research groups studied the potency of imaging and treatment of drug-resistant pathogens using radiolabeled antimicrobial compounds [24], and the radiopharmacy and pharmacology of cationic AMPs are well established [25]. Examples of radiolabeled natural AMPs, which have been intensively evaluated for the imaging of infections in animal models, are (recombinant) lactoferrins, defensins, histatins, and ubiquicidin [23,38,39].
Noninvasive optical imaging of staphylococcus aureus infection in vivo using an antimicrobial peptide fragment based near-infrared fluorescent probes
2013, Journal of Innovative Optical Health SciencesExploiting Albumin as a Versatile Carrier for Cancer Theranostics
2023, Accounts of Chemical ResearchCore–Shell Nanoparticle Combined with Bacterial Targeting and Antibiotic Loading for Bacteria Tracing and Clearing
2023, Advanced NanoBiomed Research