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目的 研究重组抗肿瘤融合蛋白疫苗热激蛋白65-黏蛋白1(HSP65-MUC1)在恒河猴和荷瘤小鼠体内的药代动力学.方法 采用放射性125I标记HSP65-MUC1,6只恒河猴随机分为iv与sc 40μg·kg1-组,sc 40 μg·kg-1组同时设为重复给药组,每2周给药1次,共3次.sc组恒河猴sc给予[125I]HSP65-MUC1 40 μg·kg-1后,于每次给药后0,1,2,4,8,12,24,36,48和72 h采集血样,iv组恒河猴iv给予[125I]HSP65-MUC1 40μg·kg-1后,于0,1,5,15,30,45 min和1,2,3,4,8,12,24 h时采集血样,应用分子排阻色谱法测定[125I]HSP65-MUC1血清中的浓度.25只荷瘤小鼠随机分为0.5,1.5,4,8和24 h给药组,小鼠在sc给予[125I]HSP65-MUC1 550 μg·kg-1后,分别于设定时间取得各组织血清和尿液;采用三氯乙酸沉淀法测定[125I]HSP65-MUG1肝、肾和肺等组织中的含量.结果 恒河猴sc给予HSP65-MUC1后绝对生物利用度为38.33%.恒河猴重复给药3次后血药谷浓度未见增高,蓄积因子(AUC3/AUC1)=1.17±0.25,与第一次给药相比无统计学差异.荷瘤小鼠sc给予HSP65-MUC1后组织分布有明显特点,浓度最高部位在局部引流淋巴结.在其他免疫组织如胸腺和脾中浓度虽不高,但达峰后下降趋势较缓慢.而在血液和其他血容量大的组织如心,肝,肺中浓度并不高,且达峰浓度后浓度下降很陕.在肿瘤组织中浓度也较低.该疫苗主要经肾排泄.结论 恒河猴sc给予HSP65-MUC1后生物利用度为38.33%,重复给药后疫苗在体内无蓄积.荷瘤小鼠sc后疫苗在局部引流淋巴结含量最高,在肿瘤组织中含量不高.该疫苗在免疫学组织如胸腺和脾中达峰浓度后的下降趋势较缓慢.“,”OBJECTIVE To study the pharmacokinetics of heat shock protein 65-mucin 1 (HSP65-MUC1) recombinant fusion protein vaccine in Macaca mulatta monkeys and tumor-bearing mice. METHODS HSP65-MUC1 was labeled by radioactive isotope 125I. M. mulatta monkeys were randomly divided into sc and iv administration groups. Simultaneously, sc administration group was designed as a multiple dose group in which M. mulatta monkeys were sc given [ 125I] HSP65-MUC1 40 μg·g-1, once every 2 weeks for a total of 3 times. Size exclusion chromatography ( SEC) was used to determine concentrations of HSP65-MUC1 in serum samples. The tumor-bearing mice were randomly divided into 0.5, 1.5, 4, 8 and 24 h groups. Mice were sc given [125I] HSP65-MUC1 550 μg·kg-1, tissues were collected and tissue distribution of [125I] HSP65-MUC1 in tumor-bearing mice was studied using trichloroacetic acid (TCA) precipitation method. RESULTS The absolute bioavailability of [125I]HSP65-MUC1 was 38.33% after M. mulatta monkeys were sc given [125I]HSP65-MUC1. In multiple dose group, concentrations of [125I]HSP65-MUC1 after the third dose administration was compared to that of the first dose administration. The accumulation factor (AUC3/AUC1) was 1.17 ±0.25. Distribution of [ 125I]HSP65-MUC1 was significantly different compared with general polypeptide and protein drugs after sc in tumor-bearing mice. The concentration in lymph nodes was the highest. The concentration in other immune tissues, such as thymus and spleen, were not relatively high, but their declined tendency was slow after reaching the peak concentration (cmax ). However, the concentrations in the serum and some other tissues with a large blood volume, such as the heart, liver, and lung, were relatively low and declined quickly after reaching cmax. Its level in the tumor was not very high. [125 I] HSP65-MUC1 was excreted mainly by the kidneys. CONCLUSION The bioavailability of [125I]HSP65-MUC1 is 38.33% after sc administration in M. mulatta. After multiple-dose administration, the vaccine does not accumulate in the body, whose concentration is the highest in lymph nodes after [1251] HSP65-MUC1 was sc given in tumor-bearing mice, but is not very high in tumor. Besides, the vaccine declined tendency is slow after reaching cmax in immune tissues such as thymus and spleen compared with other tissues with a large blood volume.