中文摘要：

以人血清白蛋白为连接剂和药物载体,制备了人血清白蛋白-叶酸偶联物（HSA-FA）,其偶联数n≈3.以SnCl2·H2O作为还原剂,采用直接标记法制备99mTc-HSA-FA标记配合物,其放射化学纯度大于90%.体外细胞结合实验结果表明,99mTc-HSA-FA能被叶酸受体高表达的KB细胞特异性摄取.荷瘤S180小鼠体内生物分布的研究结果表明,与99mTc-HSA相比,99mTc-HSA-FA在小鼠体内的生物分布发生明显变化,其在肿瘤中的放射性浓集明显增加（t=12.03,P〈0.05）,并表现出较高的摄取[（4.37±1.12）%ID/gat1h]和滞留[（3.40±0.69）%ID/gat4h];经注射过量稳定配体使99mTc-HSA-FA受到抑制后,其在肿瘤和肾中的摄取明显降低（t=24.17和17.87,P〈0.05）,表明人血清白蛋白-叶酸偶联物对叶酸受体有特异性结合.

英文摘要：

The folate receptor is a useful target that has been exploited for tumor-specific drug delivery.In this study,human serum albumin-folate conjugate（HSA-FA） was prepared with HSA as the linker and drug carrier.Coupling degree of the conjugate show that one molecule of HSA is loaded with about three folic acid molecules.The corresponding 99mTc-complex was successfully obtained by SnCl2 ·2H2O as reducing agent.The radiochemical purity of the product was above 90% by TLC and HPLC.The results of in vitro experiments show that the complex bound the KB tumor cells specifically.In vivo study of 99mTc-HSA-FA was performed in Kunming mice bearing S180 tumor.Compared with 99mTc-HSA,the biodistribution of 99mTc-HSA-FA was different and the tumor uptake was significantly increased（t = 12.03,P 0.05）.99mTc-HSA-FA showed a high accumulation[（4.37 ± 1.12） % ID/g at 1h]and good retention[（3.40 ± 0.69） % ID/g at 4 h]in tumor.The ratios of tumor/blood and tumor/muscle increased with time and were 0.45 and 4.28 at 1 h post injection,and reached 0.76 and 5.00 at 4 h post injection,respectively.After blocking with the cold ligand,the uptakes of kidney and tumor were lower than the control（t = 24.17 and 17.87,respectively,P 0.05）.These results indicate the specific binding of HSA-FA to the folate receptor.