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用于感染检测的放射性标记抗菌肽。

Radiolabelled antimicrobial peptides for infection detection.

作者信息

Lupetti Antonella, Welling Mick M, Pauwels Ernest K J, Nibbering Peter H

机构信息

Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Lancet Infect Dis. 2003 Apr;3(4):223-9. doi: 10.1016/s1473-3099(03)00579-6.

Abstract

It can be difficult to establish whether a febrile episode in a patient is suggestive of an infectious or non-infectious cause. Besides clinical history, physical examination, and laboratory assays, scintigraphic imaging of bacterial and fungal infections using antimicrobial peptides labelled with technetium-99m (99mTc) can be useful. Key to this latter approach is that some of these peptides accumulate at sites of infection but not in sterile inflammatory lesions, because of their preferential binding to bacteria and fungi over mammalian cells. Here we report on imaging of infections with these peptides in laboratory animals. On the basis of their favourable binding characteristics, fast and easy penetration into the infected area, and rapid clearance from the circulation (half-life approximately 30 min) via the kidneys, several 99mTc-antimicrobial peptides have been selected that distinguish infectious foci from sites of sterile inflammation. Accumulation of 99mTc-antimicrobial peptides at sites of experimental infection correlated well with the number of viable bacteria/yeasts present. This finding allowed us to monitor with 99mTc-antimicrobial peptides the efficacy of antimicrobial therapy in animals with experimental infections. In conclusion, non-microbicidal amounts of 99mTc-antimicrobial peptides are promising candidates for the scintigraphic imaging of bacterial/fungal infections and for monitoring the efficacy of antimicrobial therapy in patients.

摘要

很难确定患者的发热发作是提示感染性还是非感染性病因。除了临床病史、体格检查和实验室检测外,使用用锝-99m(99mTc)标记的抗菌肽对细菌和真菌感染进行闪烁成像可能会有所帮助。后一种方法的关键在于,这些肽中的一些会在感染部位积聚,但不会在无菌性炎症病变中积聚,因为它们与细菌和真菌的结合优先于哺乳动物细胞。在此,我们报告了在实验动物中用这些肽对感染进行成像的情况。基于其良好的结合特性、快速且容易渗透到感染区域以及通过肾脏从循环中快速清除(半衰期约30分钟),已选择了几种99mTc-抗菌肽,它们能够区分感染灶和无菌性炎症部位。99mTc-抗菌肽在实验感染部位的积聚与存在的活细菌/酵母数量密切相关。这一发现使我们能够用99mTc-抗菌肽监测实验感染动物中抗菌治疗的疗效。总之,非杀菌量的99mTc-抗菌肽有望用于细菌/真菌感染的闪烁成像以及监测患者抗菌治疗的疗效。

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