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本研究比较了~(125)标记的氨甲喋呤-人血清白蛋白-单抗79(MTX-HSA-McAb79)和氨甲喋呤-人血清白蛋白(MTX-HSA)两种结合物的血浓度及在肝、脾、肾等重要脏器的组织分布。发现前者的生物利用度大、血的清除率低、且肝脏等重要代谢器官对它的摄取也低。 在MTX-HSA-McAb79结合物的稳定性研究中,首先采用纸层析法及荧光分光光度法分别证明结合物中酰胺键在体内外均具有良好的稳定性;其次采用SDS-PAGE结合放射自显影术,再通过薄层扫描定量,研究了结合物中二硫键的稳定程度。结果表明:二硫键相当不稳定,腹腔注射后1h即有60.5％的二硫键断裂,24h则高达92.9％。r-扫描显示MTX-HSA-McAb79在肿瘤部位的浓集不理想,这与二硫键稳定性试验的结果是一致的。探索新的交联剂和交联方法,增加结合物在体内的稳定性将是今后的目标之一。
This study compared the blood concentrations of the two conjugates of methotrexate-human serum albumin-monoclonal antibody 79 (MTX-HSA-McAb79) and methotrexate-human serum albumin (MTX-HSA) Spleen, kidney and other important organs of the organization. The former is found to have high bioavailability, low blood clearance, and low uptake by important metabolic organs such as the liver. In the study of the stability of MTX-HSA-McAb79 conjugates, the paper first confirmed the good stability of the amide bond in the conjugates both in vitro and in vivo by using paper chromatography and fluorescence spectrophotometry. Secondly, Development, and then quantified by thin layer scanning to study the stability of disulfide bonds in the conjugate. The results showed that the disulfide bond was rather unstable, 60.5% disulfide bond was broken at 1 hour after intraperitoneal injection, and 92.9% at 24h. The r-scan showed that the concentration of MTX-HSA-McAb79 at the tumor site was not ideal, which is consistent with the result of the disulfide stability test. Exploring new crosslinking agents and crosslinking methods to increase the stability of the conjugate in vivo will be one of the goals for the future.