Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Detection of Fungal Infections Using Radiolabeled Antifungal Agents

Author(s): A. Lupetti, M. M. Welling, E. K. J. Pauwels, P. H. Nibbering.

Abstract:

The 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 (99mTc) and their in vivo distribution is monitored in infected mice. It has been demonstrated that 99mTc-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. 99mTc-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. albicansinfected mice could be successfully monitored using 99mTc-ubiquicidin. In conclusion, neither 99mTc-fluconazole nor the 99mTc-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 99mTc-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.

Keywords: Fluconazole, Antimicrobial peptides, Candida albicans, Aspergillus fumigatus, Technetium-99m labeling, Infection detection

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Article Details

VOLUME: 6
ISSUE: 8
Year: 2005
Page: [945 - 954]
Pages: 10
DOI: 10.2174/138945005774912753
Price: $58