炎症显像剂^99Tc^m—lomefloxacin的制备及其炎症小鼠模型体内生物学分布

Preparation and biodistribution of ^99 Tc^m-lomefloxacin in inflammatory model mice

目的建立^99Tc^m标记洛美沙星（lomefloxacin）的方法，评价^99Tc^m-lomefloxacin体外结合能力和炎症小鼠模型体内生物学分布特征。方法制备^99Tc^m-lomefloxacin并用薄层层析法（TLC）进行鉴定。在标记过程中，研究SnCl2·2H2O、lomefloxacin、pH、温度和反应时间等因素对标记结果的影响。测定标记化合物的稳定性、脂水分配系数和体外细菌特异性结合能力。制备小鼠炎症模型30只，用抽签法分为6组，经尾静脉注入^99Tc^m-lomefloxacin，分别于0．5，1，2，4，6h各处死1组小鼠，取出重要脏器组织测量放射性，计算每克组织百分注射剂量率（％ID／g）及炎症肌肉与正常肌肉放射性比值（T／NT），观察其体内分布特征；另一组行放射自显影，观察显像效果。采用Concise Statistics 10．3软件，组间差异比较行方差分析。结果^99Tc^m-lomefloxacin的标记率和放化纯为97．5％，室温放置6h内标记率和放化纯均〉95％。^99Tc^m-lomefloxacin为脂溶性物质，与金黄色葡萄球菌的体外结合呈现良好的时间和浓度梯度变化。^99Tc^m-lomefloxaein在炎症模型小鼠体内主要分布于炎症组织及肾、肝、脾中，炎症肌肉与对侧正常肌肉的放射性比较，差异有统计学意义（F=9．19，P〈0．05），T／NT比值峰值为4．07±1．05，给药后2h的显像质量最佳。结论^99Tc^mlomefloxacin标记简单、标记率和放化纯高、稳定性好、体外结合分析和体内生物学分布具有比较理想的炎症显像剂特性。

Objective The study of ^99Tc^m-ciprofloxaein, a fluoroqulnolones antibiotic, as a tracer for infection and inflammation imaging has been reported. The aim of this study was to investigate the radio- labeling and biodistribution of lomefloxacln （fluoroquinolones analogue） as an inflammatory imaging agent. Methods ^99Tc^m-lomefloxacin was prepared and it underwent quality control with thin layer chromatography （TLC）. The different labeling conditions werc compared. The radiochemical purity, labeling efficiency, stability and lipld/water partition coefficient of ^99Tc^m-lomefloxacin were measured. The binding activities of ^99Tc^m-lomefloxaein with Staphylococci aureus （S. aureus） in vitro were tested. ^99Tc^m-lomefloxacin was injected through tail vein in the S. aureus-indueed inflammatory model mice. The mice were sacrificed and their blood, inflammatory muscles, major organs were taken out at different time after tracer injection. Then the radioactivity count of these samples was measured to observe biodistribution. Whole-body radioautographic images were obtained with storage phosphor screen system. Variance analysis using Concise Statistics 10.3 software was performed. Results ^99Tc^m-lomefloxacin was lipid-soluble with labeling efficiency of 97.5%. The radiochemical purity was more than 95% at 6 h after storing in room temperature. In vitro test ^99Tc^m-lomefloxacin showed good binding characteristic with S. aureus and was positively correlated with the colony number of S. aureus. The highest binding appeared at 1 h. In vivo ^99Tc^m-lomefloxacin apparently accumulated in inflammatory, tissues at 2 h after tracer injection with the uptake ratio of 4.07 ±1.05 in inflammatory muscles to control muscles. Whole-body autoradiography showed that all inflammation foci were visualized. Conclusion ^99Tc^m-lomefloxacin may be a novel potential agent for inflammatory imaging.