188-Re直接法标记CD45单抗及其体内生物分布研究

目的：利用188Re直接法标记CD45单抗，探讨其在正常小鼠体内的生物学分布特性。方法应用2-巯基乙醇（2-ME）还原CD45单抗分子中的二硫键形成巯基；以氯化亚锡作为188Re的还原剂，葡庚糖酸钠为中间弱配体，188Re直接标记CD45单抗；PD-10层析柱分离纯化，纸层析法测定标记率与放化纯；鉴定188Re-CD45单抗的体外稳定性；研究188Re-CD45单抗在正常小鼠体内的生物分布特性。结果188Re-CD45单抗的标记率平均为（85.25±2.63）%，PD-10柱纯化后的放化纯为（92.54±3.56）%，比活度平均为（2.06±0.07）TBq/mmol；室温下放置24 h，188Re-CD45单抗放化纯为（64.33±1.53）%；在鼠血清和生理盐水中37℃下孵育24 h后，其放化纯仍有（64.2±3.77）%和（56.7±4.16）%。小鼠体内生物分布显示，188Re-CD45单抗主要分布于肾脏和肝脏，其次是肺脏、骨骼和血液。结论188Re直接法标记CD45单抗的方法简单易行，标记率较高，具有良好的体外稳定性；188Re-CD45单抗静脉注射后，体内放射性主要经肾脏排泄，并在肝脏有较高的浓聚，符合标记抗体的体内分布规律。

Direct-radiolabeling of CD45 monoclonal antibody with rhenium-188 and its biodistribution in normal mice

Objective With direct-labeling method of CD45 McAb with 188Re, to investigate its bio-distribution character in normal mice. Methods The disulfide bond in the molecule of CD45 monoclonal antibody was reduced to form a mercapto group by the mercaptoethanol （2-ME）. The labeling was conducted by stannous chloride used as reductant of 188Re, and sodium glucoheptonate as intermediate.weak ligands, then 188Re was directly labeled CD45 mAb alone; The reaction mixture was separated and purified throuth the PD-10 column;Labeling efficiency and radiochemical purity were measured by the paper chromatography. Then stability of 188Re labeled CD45 McAb was determined in vitro. The biodistribution in the healthy Kunming mice after intravenous injection of 188Re-CD45 McAb was determined. Results The labeling efficiency of 188Re-CD45 McAb was （85.25±2.63）%, and radiochemical purity was （92.54±3.56）%. The specific activity was （2.06±0.07） TBq/mmol;The radiochemical purity of 188Re-CD45 McAb was （64.33±1.53）% after incubating 24 h in room temperature. While mixed the saline and healthy rat serum at 37℃for 24 h, the radiochemical purity was （64. 2±3. 77）%and（56. 7±4. 16）%, respectively. The biodistribution result showed that the radioactivity in body was mainly distributed in kidney and liver, followed by lung, bone and blood. Conclusion The method of direct-labeling CD45 McAb with 188Re is not only simple, but also has high labeling efficiency. 188Re-CD45 McAb has good stability in vitro. After injected intravenously, radioactive label is mainly excreted through kidneys with a higher accumulation in liver, and it accords with the in vivo kinetics characteristic of labeled antibody.