^(110m)Ag标记金属硫蛋白MT和MT-IgG的生物分布及其体内稳定性

THE BIODISTRIBUTION AND IN VIVO STABILITY OF ^(110m)Ag-LABELED METALLOTHIONEIN AND MT-IgG

本文介绍了^(110m)Ag标记金属硫蛋白MT及MT-IgG的方法,标记率几乎100％,并获得较高的比活度。^(110m)Ag(NH_3)_2^+,^(110m)Ag-MT和^(110m)Ag-MT-IsG在瑞士小鼠体内分布及代谢研究表明,^(110n)Ag(NH_3)_2^+和^(110m)Ag-MT-IgG主要经肝脏代谢,但^(110m)Ag(NH_3)_2^+比^(110m)Ag-MT-IgG浓聚得快且量大,前者代谢的速度也快些。^(110m)Ag-MT在肝脏中则呈现较平稳的代谢曲线。^(110n)Ag-MT主要是通过肾脏排泄,经尾静脉注射后1小时内,在小鼠肾脏中保持在130％ID/g以上,最大值达210％ID/g,肾脏吸收剂量则达36％ID/g。这证明,^(110n)Ag-MT和^(110m)Ag-MT-IgG在体内稳定。因此,有希望制备单克隆抗体的标记物^(110)Ag-MT-McAb用以治疗肿瘤。

110mAg labeling of metallothionein (MT) and MT-IgG in the state of Ag(NH3)2+ are carried out in 0.050mol/1 barbitone buffer with pH 8.0. All labeling yields attained approximately 100%. And specific radioactivity is as high as 12.21×106Bq/mg MT and 4.07×106Bq/mgMT-IgG, when 4.63×107 Bq/mg irradiated Ag (110mAg) is used in the experiment.Biodistribution differences of 110mAg(NH3 )2+, 110mAg-MT and 110mAg-MT-IgG in Swiss mice within 6 hours post tail i.v. injection are distinct. 110mAg(NH3)2+ and 110mAg-MT-IgG are mainly removed by liver, while 110mAg-MT accumulates in kidneys rapidly and highly. 110mAg(NH3)2+ and 110mAg-MT-IgG reach their highest uptake in liver, 69% ID/g in 30min and 65% ID/g in 45min. But 110mAg(NH3)2+ is removed much faster than 110mAg-MT-IgG.Their retention in 6 hours is 20% ID/g and 50% ID/g respectively. 110mAg-MT does not accumulate much in liver, the maximum is 30% ID/g, and its decrease is relatively slow. On the other hand, 110mAg-MT accumulates highly in kidneys, up to 210% ID/g in 20min, and maintains above 130% ID/g for one hour. In contrast, the concentrations of 110mAg(NH3)2+ and 110mAg-MT-IgG in kidneys are low, only 10%ID/g and 6%ID/g at the highest levels. With regard to the blood clearance of the three radiolabeled compounds, 110mAg-MT is the fastest, and 110mAg(NH3)2+ maintains relatively high level in blood. The different pharmacokinetics of 110mAg(NH3)2+, 110mAg-MT and 110mAg-MT-IgG, indicates that 110mAg radiolabeling of MT and its conjugated IgG are stable in vivo. This preliminary study on the labeling of IgG with 110mAg would be of value in developing MT as a bifunctional chelating agent for 111Ag in radioimmunotherapy.