ASGP受体显像剂能够评价肝脏的形态和功能，有助于肝脏疾病的早期诊断并对其功能状态进行准确的评价。本论文在参考相关文献的基础上，主要进行了以下几部分工作：1. 合成了2-亚氨基-2-甲氧基乙基-1-硫代-β-D-半乳吡喃糖苷，产物均经过红外、核磁、元素分析等方法予以鉴定。通过在人血白蛋白分子上引入半乳糖残基得到新乳糖白蛋白（NGA），再与DTPA环酐反应得到GSA；或首先通过DTPA环酐将双功能连接剂引入，再引入硫代半乳糖残基，得到GSA。两种方法均可靠有效。通过紫外法、苯酚-硫酸法测定所得GSA的糖密度在30～40的范围之内。2. 通过摸索99mTc标记GSA的条件，得到了标记率大于95%的99mTc-GSA。在此基础上进行了GSA药盒化的研究，成功制备了GSA的一步法冻干药盒；并参考中国药典（2005版，二部）自行制订了药盒的质量标准，对所得的GSA药盒进行了质量控制。药盒标记简单可靠，可稳定保存6个月以上。3. 在正常小鼠体内对99mTc-GSA的生物分布进行了研究，并进行了抑制实验。结果表明99mTc-GSA在肝脏中有较高的摄取，30min仍有（73.44±5.01）%ID/g，与99mTc-NGA相比有较好的肝脏保留，抑制实验也说明99mTc-GSA对ASGP受体具有亲和性；选取了三种不同的方式分别建立了化学性肝损伤、淤胆性肝损伤、肝癌肝损伤模型，结果表明，在三种肝损伤模型中，99mTc-GSA在肝脏中的摄取与对照组性比均有显著降低（P<0.05）；选用新西兰兔，进行了SPECT显像研究，显像结果清晰，为进一步临床研究奠定基础。4. 选取SATP引入新乳糖白蛋白NGA上，制备了含双功能连接剂DMP的一种全新的配体DMP-NGA，并用99mTc标记得到了99mTc-DMP-NGA，经HPLC纯化后，放化纯大于95%。小鼠体内生物分布的研究显示其优良的生物性能，与99mTc-GSA相比，有较高的肝脏初始摄取，血液本底明显降低，肝/血比值达到83.4。在腹腔其它脏器的摄取也有所下降。5. 以HYNIC作为双功能连接剂，制备了HYNIC-NGA，选取三种共配体进行了标记，得到三种配合物99mTc-tricine/HYNIC-NGA、99mTc-bicine/HYNIC-NGA、99mTc-HEDTA /HYNIC-NGA，经凝胶柱纯化后，放化纯均大于95%。生物分布的研究表明三种配合物均有较好的生物性能，其中99mTc-tricine/HYNIC-NGA、99mTc-HEDTA/HYNIC-NGA有较高的肝脏摄取，除肝脏外其它脏器的摄取与99mTc-GSA相比有明显降低。

ASGP receptor imaging agent can assess the anatomy and function of the liver, help the early diagnosis of hepatic diseases and functional status accurate evaluation. The main aspects of this thesis were described as following:1. 2-imino-2-methoxyethyl-thio-galactose was synthesized and characterized by IR, NMR, elemental analysis. The ligand GSA was synthesized by frist introducing galactosyl units (2-imino-2-methoxyethyl-thio-galactose) to human serum albumin (HSA), and then coupling bifunctional chelator DTPA, or synthesized by frist introducing bifunctional chelator DTPA to HSA via DTPA anhydride, and then coupling galactosyl units to DTPA-HSA. Both methods are reliable and effective. The average number of galactose groups per GSA molecule was about 30 to 40.2. GSA was labeled with technetium-99m by using SnCl2 as reductant and the labeling conditions of 99mTc-GSA were optimized, and the labeling yields in excess of 95%. Lyophilized kit of GSA was developed for instant preparing of 99mTc-GSA. Quality control of the GSA kit was studied according to the Pharmacopoeia and quality standard. The preperation of 99mTc-GSA by using lyophilized kit is instant and reliable. The shelf life is no less than 6 months.3. In vivo biodistribution of 99mTc-GSA was investigated in both normal mice and liver injure model. 99mTc-GSA showed high liver uptake in normal mice, about (73.44±5.01)%ID/g at 30 min after injection. 99mTc-GSA showed better retention versus 99mTc-NGA. Select three different liver injure mice models included hepatic fibrosis, hepatic cholestasis, and liver cancer. Results show that liver uptake of 99mTc-GSA in three models were significantly lower than that of in normal mice (P<0.05). The good quality of SPECT imaging study in rabbits affords the opportunity of liver receptor imaging for further routine clinical research.4. The SATP was coupling with galactosyl-neoglycoalbumin (NGA), a novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared. The DMP-NGA was labeled with technetium-99m, and the radiochemical purity in excess of 95% after purified with HPLC. In vivo biodistribution showed that 99mTc-DMP-NGA had very high initial liver uptake (99.35%ID/g) with good retention. It had higher initial liver uptake and much lower blood uptake than that of 99mTc-GSA. The liver/blood ratio reached 83.4 at 30 min post-injection time. The uptakes in other organs in the abdomen were also slightly lower than that of 99mTc-GSA.5. Bifunctional coupling agent HYNIC was introduced and HYNIC-NGA was prepared. The 99mTc radiolabeling of HYNIC-NGA with three different coligands to give the complexes: 99mTc-tricine/HYNIC-NGA, 99mTc-bicine/HYNIC-NGA and 99mTc-HEDTA/HYNIC-NGA, respectively. The radiochemical purity could reach 95% after purified with size exclusion column. The biodistribution of the three complexes resulted that they have good biological properties. 99mTc-tricine/HYNIC-NGA and 99mTc-HEDTA/HYNIC-NGA shows high uptake in the liver. The uptake in other organs was decreased significantly when compared with 99mTc-GSA.