Lupetti A, Welling M M, Pauwels E K J, Nibbering P H
Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, P.O. Box 9600, C4-Q Room 75, 2300 RC, Leiden, The Netherlands.
Curr Drug Targets. 2005 Dec;6(8):945-54. doi: 10.2174/138945005774912753.
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 ((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.
抗真菌治疗的结果取决于治疗开始时感染的进展情况。不幸的是，由于免疫功能低下患者真菌感染的非特异性临床症状以及当前真菌学诊断测试的低敏感性，大多数患者在真菌感染进展到相当程度后才被诊断出来。本综述将重点介绍当前的真菌诊断技术，并将聚焦于用于在小鼠中特异性检测真菌感染的闪烁成像方法。为此，抗真菌成分（如氟康唑和抗真菌肽）用例如锝-99m（99mTc）进行放射性标记，并在感染小鼠中监测它们的体内分布。已经证明，99mTc-氟康唑是检测小鼠白色念珠菌感染的优良示踪剂，因为它能将这些感染与细菌感染和无菌性炎症区分开来。然而，这种放射性药物在检测小鼠烟曲霉感染方面效果不佳。源自抗真菌肽/蛋白质的99mTc-肽，如人泛菌素和乳铁蛋白，在小鼠中可以将白色念珠菌和烟曲霉感染与无菌性炎症区分开来，但不能与细菌感染区分开来。此外，使用99mTc-泛菌素可以成功监测氟康唑在白色念珠菌感染小鼠中的疗效。总之，99mTc-氟康唑和所测试的99mTc-肽都不是真菌感染的最佳示踪剂。尽管如此，由于早期开始念珠菌血症的抗真菌治疗可降低其高死亡率，99mTc-氟康唑闪烁成像的阳性结果具有临床意义。最后，应考虑其他（放射性标记的）抗真菌药物，如伏立康唑、卡泊芬净、抗真菌植物或昆虫防御素，是否可用于检测真菌感染的可能性。
