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用 Ga-68 标记的吡咯并喹啉啉用于正电子发射断层扫描的铜绿假单胞菌感染成像。

Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography.

机构信息

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

出版信息

Sci Rep. 2018 Oct 24;8(1):15698. doi: 10.1038/s41598-018-33895-w.

DOI:10.1038/s41598-018-33895-w
PMID:30356077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6200719/
Abstract

Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of life-threatening nosocomial infections. Novel strategies for the development of new antibacterial treatments as well as diagnostic tools are needed. One of the novel diagnostic strategies for the detection of infection could be the utilization of siderophores. Siderophores are low-molecular-weight chelators produced by microbes to scavenge essential iron. Replacing iron in siderophores by suitable radiometals, such as Ga-68 for positron emission tomography (PET) imaging, opens approaches for targeted imaging of infection. Here we report on pyoverdine PAO1 (PVD-PAO1), a siderophore produced by P. aeruginosa, labelled with Ga-68 for specific imaging of Pseudomonas infections. PVD-PAO1 was labelled with Ga-68 with high radiochemical purity. The resulting complex showed hydrophilic properties, low protein binding and high stability in human serum. In vitro uptake of Ga-PVD-PAO1 was highly dependent on the type of microbial culture. In normal mice Ga-PVD-PAO1 showed rapid pharmacokinetics with urinary excretion. PET imaging in infected animals displayed specific accumulation of Ga-PVD-PAO1 in infected tissues and better distribution than clinically used F-fluorodeoxyglucose (F-FDG) and Ga-citrate. Ga-68 labelled pyoverdine PAO1 seems to be a promising agent for imaging of P. aeruginosa infections by means of PET.

摘要

铜绿假单胞菌是一种日益流行的机会性病原体，可引起多种危及生命的医院获得性感染。需要开发新的抗菌治疗策略和诊断工具。感染检测的新诊断策略之一可能是利用铁载体。铁载体是微生物产生的低分子量螯合剂，用于掠夺必需的铁。用合适的放射性金属（如 Ga-68 用于正电子发射断层扫描（PET）成像）取代铁载体中的铁，为感染的靶向成像开辟了途径。在这里，我们报告了铜绿假单胞菌产生的铁载体吡咯并喹啉（PVD-PAO1），用 Ga-68 标记以特异性成像铜绿假单胞菌感染。PVD-PAO1 用 Ga-68 标记，具有高放射化学纯度。所得复合物具有亲水性、低蛋白结合性和在人血清中的高稳定性。Ga-PVD-PAO1 的体外摄取高度依赖于微生物培养物的类型。在正常小鼠中，Ga-PVD-PAO1 表现出快速的药代动力学特性，尿液排泄迅速。感染动物的 PET 成像显示 Ga-PVD-PAO1 在感染组织中的特异性积聚，并且分布优于临床使用的 F-氟脱氧葡萄糖（F-FDG）和 Ga 柠檬酸盐。Ga-68 标记的吡咯并喹啉似乎是通过 PET 成像铜绿假单胞菌感染的有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/a3cc1040b660/41598_2018_33895_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/1a244d2b6f56/41598_2018_33895_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/35e44c529492/41598_2018_33895_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/8f6768709680/41598_2018_33895_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/b9926cb75b39/41598_2018_33895_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/e15e14705448/41598_2018_33895_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/a007407fb0ce/41598_2018_33895_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/a3cc1040b660/41598_2018_33895_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/1a244d2b6f56/41598_2018_33895_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/35e44c529492/41598_2018_33895_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/8f6768709680/41598_2018_33895_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/b9926cb75b39/41598_2018_33895_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/e15e14705448/41598_2018_33895_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/a007407fb0ce/41598_2018_33895_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4c/6200719/a3cc1040b660/41598_2018_33895_Fig7_HTML.jpg

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