Dutta Jyotibon, Baijnath Sooraj, Somboro Anou M, Nagiah Savania, Albericio Fernando, de la Torre Beatriz G, Marjanovic-Painter Biljana, Zeevaart Jan Rijn, Sathekge Mike, Kruger Hendrik G, Chuturgoon Anil, Naicker Tricia, Ebenhan Thomas, Govender Thavendran
Catalysis and Peptide Research Unit, School of Health Sciences and School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.
Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.
Chem Biol Drug Des. 2017 Oct;90(4):572-579. doi: 10.1111/cbdd.12980. Epub 2017 Apr 17.
Bacterial infections are a major concern in the human health sector due to poor diagnosis and development of multidrug-resistant strains. PET/CT provides a means for the non-invasive detection and localization of the infectious foci; however, the radiotracers available are either cumbersome to prepare or their exact contribution toward the imaging is not yet established. Human antimicrobial peptides are of interest for development as PET radiotracers as they are an integral component of the immune system, non-immunogenic toward the recipient, and show selectivity toward pathogens such as bacteria. Herein we report on the potential of LL37, a human cathelicidin antimicrobial peptide, as a radiotracer for bacterial imaging. Bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid was utilized to functionalize the antimicrobial peptide, which in turn was capable of chelating gallium. The synthesized Ga-CDP1 showed bacterial selectivity and low affinity toward hepatic cells, which are favorable characteristics for further preclinical application.
由于诊断困难以及多重耐药菌株的出现，细菌感染成为人类健康领域的一个主要问题。正电子发射断层扫描/计算机断层扫描（PET/CT）为感染灶的无创检测和定位提供了一种手段；然而，现有的放射性示踪剂要么制备繁琐，要么其对成像的确切贡献尚未明确。人类抗菌肽作为PET放射性示踪剂具有开发价值，因为它们是免疫系统的一个组成部分，对接受者无免疫原性，并且对细菌等病原体具有选择性。在此，我们报告人源杀菌肽LL37作为细菌成像放射性示踪剂的潜力。利用双功能螯合剂1,4,7-三氮杂环壬烷-1-戊二酸-4,7-乙酸对该抗菌肽进行功能化，进而使其能够螯合镓。合成的Ga-CDP1表现出细菌选择性以及对肝细胞的低亲和力，这些都是有利于进一步临床前应用的特性。
