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(99m)Tc-克林霉素的制备、生物分布及闪烁显像评估:一种感染显像剂

Preparation, biodistribution, and scintigraphic evaluation of (99m)Tc-clindamycin: an infection imaging agent.

作者信息

Hina Saira, Rajoka Muhammad Ibrahim, Roohi Samina, Haque Asma, Qasim Muhammad

机构信息

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan.

Isotope Production Division, PINSTECH Nilore, Islamabad, Pakistan.

出版信息

Appl Biochem Biotechnol. 2014 Oct;174(4):1420-1433. doi: 10.1007/s12010-014-1075-z. Epub 2014 Aug 12.

Abstract

Bacterial infection is found to be the cause of death throughout the world. Nuclear medicine imaging with the help of radiopharmaceuticals has great potential for treating infections. In the present work, clindamycin, a lincosamide antibiotic, was labeled with technetium-99 m (~380 MBq). Clindamycin has been proven to be efficient for treating serious infections caused by bacteria such as Staphylococcus aureus. Quality control, characterization, biodistribution, and scintigraphy of radiolabeled clindamycin were done, and labeling efficiency was determined by ascending paper chromatography. More than 95 % labeling efficiency with technetium-99 m ((99m)Tc) was achieved at pH 6-7 while using 2.5-3 μg SnCl2 · H2O as a reducing agent and 100 μg of ligand at room temperature. The characterization of the compound was performed by using electrophoresis, HPLC and shake flask assay. Electrophoresis indicates the neutral behavior of (99m)Tc-clindamycin. HPLC analysis confirms the single specie of the labeled compound, while shake flask assay confirms high lipophilicity. The biodistribution studies of (99m)Tc-clindamycin were performed Sprague Dawley rats bearing bacterial infection. Scintigraphy and biodistribution studies showed a high uptake of (99m)Tc-clindamycin in the liver, heart, lung, and stomach as well as at S. aureus-infected sites in rabbits.

摘要

研究发现细菌感染是全球范围内的死因。借助放射性药物的核医学成像在治疗感染方面具有巨大潜力。在本研究中,将克林霉素(一种林可酰胺类抗生素)用99m锝(~380 MBq)进行标记。克林霉素已被证明对治疗由金黄色葡萄球菌等细菌引起的严重感染有效。对放射性标记的克林霉素进行了质量控制、表征、生物分布和闪烁扫描,并通过上行纸色谱法测定标记效率。在室温下,以2.5 - 3 μg二水合氯化亚锡作为还原剂、100 μg配体,在pH 6 - 7条件下,99m锝(99mTc)的标记效率超过95%。通过电泳、高效液相色谱和摇瓶试验对该化合物进行表征。电泳表明99mTc - 克林霉素呈中性。高效液相色谱分析证实标记化合物为单一物种,而摇瓶试验证实其具有高亲脂性。在患有细菌感染的斯普拉格 - 道利大鼠身上进行了99mTc - 克林霉素的生物分布研究。闪烁扫描和生物分布研究表明,99mTc - 克林霉素在肝脏、心脏、肺、胃以及兔的金黄色葡萄球菌感染部位有高摄取。

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