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Detection of fungal infections using radiolabeled antifungal agents
No full textThe outcome of antifungal therapy depends on the progression of the infection at the start of therapy. Unfortunately, most patients are diagnosed once the fungal infection has progressed considerably as a result of the non-specific clinical signs of fungal infections in immunocompromised patients and the poor sensitivity of current mycological diagnostic tests. This review will highlight current fungal diagnostic techniques and will focus on scintigraphic methods for the specific detection of fungal infections in mice. For this purpose, antifungal components (e.g. fluconazole and antifungal peptides) are radiolabeled e.g. with technetium-99m ((99m)Tc) and their in vivo distribution is monitored in infected mice. It has been demonstrated that (99m)Tc-fluconazole is an excellent tracer to detect Candida albicans infections in mice as it distinguishes these infections from bacterial infections and sterile inflammations. However, this radiopharmaceutical only poorly detects infections with Aspergillus fumigatus in mice. (99m)Tc-peptides derived from antifungal peptides/proteins, such as human ubiquicidin and lactoferrin, can distinguish C. albicans and A. fumigatus infections from sterile inflammations, but not from bacterial infections, in mice. Furthermore, the efficacy of fluconazole in C. albicans-infected mice could be successfully monitored using (99m)Tc-ubiquicidin. In conclusion, neither (99m)Tc-fluconazole nor the (99m)Tc-peptides tested are optimal tracers for fungal infections. Nonetheless, since early initiation of antifungal therapy for candidemia reduces its high mortality rate, a positive result with (99m)Tc-fluconazole scintigraphy is of clinical relevance. Finally, the possibility that other (radiolabeled) antifungal agents, e.g. voriconazole, caspofungin, antifungal plant or insect defensins, can be useful for detection of fungal infections should be considered
Technetium-99m labelled antimicrobial peptides and anti-infectives for the detection of bacterial and Candida albicans infections.
No full textInfection detection in mice using 99mTc-labeled HYNIC and N2S2 chelate conjugated to the antimicrobial peptide UBI 29-41
No full textEarlier we reported that UBI 29-41, a synthetic peptide corresponding to residues 29-41 of human ubiquicidin, directly labeled with technetium-99m ((99m)Tc-UBI 29-41) distinguishes bacterial and fungal infections from sterile inflammations in animals. This study was undertaken to evaluate the radiochemical and biological characteristics of (99m)Tc-UBI 29-41 labeled through the intermediacy of a HYNIC or N(2)S(2) moiety, which were introduced at the N-terminus of UBI 29-41 during solid phase synthesis, with (99m)Tc-UBI 29-41. Methods were as follows: UBI 29-41 and HYNIC- or N(2)S(2)-conjugated peptide were labeled with technetium-99m. Preparations of these radiolabeled UBI 29-41 were purified by HPLC and Sep-Pak. Next, the stability of these tracers in human serum was challenged for 24 hours and their in vitro binding to bacteria assessed. Using scintigraphy up to 2 hours after injection of the tracer and ex vivo countings at the last interval we evaluated the ability of the three tracers to detect bacterial infections in mice inoculated with 2 x 10(7) viable Staphylococcus aureus or Klebsiella pneumoniae as well as their biodistribution. We observed the following results: HPLC analysis of purified (99m)Tc-HYNIC-UBI 29-41, (99m)Tc-UBI 29-41 and (99m)Tc-N(2)S(2)-UBI 29-41 revealed that within 60 minutes >90% of the radioactivity was associated with the peptide. In addition, the stability of these radiolabeled UBI 29-41 peptides in human serum was excellent. All three tracers bound equally well to bacteria in vitro. After intravenous injection into mice with an experimental bacterial infection (99m)Tc-HYNIC-UBI 29-41 and (99m)Tc-UBI 29-41 were rapidly removed from the circulation mainly by renal clearance (at t = 120 minutes approximately 60% of the injected dose/gram tissue; % ID/g). In contrast, (99m)Tc-N(2)S(2)-UBI 29-41 was removed mainly by the liver (t = 120 minutes; 52% ID/g) showing deposits in the intestines (t = 120 minutes; 31% ID/g) and to a lesser extent by renal clearance (19% ID/g). All three tracers rapidly detected bacterial infections in mice and highest accumulation (target-to-nontarget ratios between 3.2 and 3.6 and between 2.9 and 4.4 for infections with S. aureus and K. pneumoniae, respectively) was found at 2 hours after injection of the tracer. In conclusion, purified (99m)Tc-HYNIC-UBI 29-41 and (99m)Tc-N(2)S(2)-UBI 29-41 were as effective as (99m)Tc-UBI 29-41 in detecting infections in mice injected intramuscularly with bacteria. However, (99m)Tc-N(2)S(2)-UBI 29-41 should not be advised for the imaging of abdominal infections as this tracer, in contrast to the other tracers, is cleared via the liver and intestines
Imaging of infections with Candida albicans with 99mTc-labelled antimicrobial peptides and the antifungal agent fluconazole.
No full textImaging of fungal infections with 99mTc-labelled fluconazole and antimicrobial peptides.
No full textRadiochemical characteristics and biological testing of technetium-99m labelled antimicrobial cationic peptides for infection detection.
No full textRadiochemical characteristics and infection imaging with UBI 29-41 peptide labelled directly and indirectly with 99mTechnetium.
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Internal thiols and reactive oxygen species in the candidacidal activity exerted by a N-terminal peptide of human lactoferrin.
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