Arano Y, Mukai T, Uezono T, Wakisaka K, Motonari H, Akizawa H, Taoka Y, Yokoyama A
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Nucl Med. 1994 May;35(5):890-8.
Since the lysosome is a common organelle for protein digestion, pursuing the fate of radiolabeled metabolites after lysosomal proteolysis in liver cells is ideal to evaluate bifunctional chelating agents (BCAs).
We used galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) as carrier proteins for hepatic parenchymal and nonparenchymal cells, respectively. These proteins were labeled with 111In using 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA) as a model.
NGA-SCN-Bz-EDTA-111In exhibited rapid accumulation in the hepatic parenchymal cells, followed by hepatobiliary excretion of the metabolites with an elimination rate that was faster and much slower than that of NGA-DTPA-111In and NGA-131I, respectively. This metabolite represented all the radioactivity registered in the liver at 1 hr postinjection. Subcellular distribution studies indicated the metabolites were located only in the lysosome fraction, and the difference in elimination rates of the metabolites from the lysosome fraction was responsible for the variations in radioactivity clearance from the cells.
The biological characteristics of radiolabeled metabolites play a critical role in eliminating the radiolabel from liver cells. The present method portrays a highly useful model to pursue the fate of radiolabeled metabolites in the liver.
由于溶酶体是蛋白质消化的常见细胞器，追踪肝细胞溶酶体蛋白水解后放射性标记代谢物的命运是评估双功能螯合剂（BCA）的理想方法。
我们分别使用半乳糖基-新糖白蛋白（NGA）和甘露糖基-新糖白蛋白（NMA）作为肝实质细胞和非实质细胞的载体蛋白。这些蛋白质用1-(4-异硫氰酸苄基)乙二胺四乙酸（SCN-Bz-EDTA）作为模型进行111In标记。
NGA-SCN-Bz-EDTA-111In在肝实质细胞中迅速积累，随后代谢物经肝胆排泄，其消除速率分别比NGA-DTPA-111In和NGA-131I的消除速率更快和更慢。这种代谢物代表了注射后1小时肝脏中记录的所有放射性。亚细胞分布研究表明，代谢物仅位于溶酶体部分，溶酶体部分代谢物消除速率的差异导致细胞放射性清除的变化。
放射性标记代谢物的生物学特性在从肝细胞中消除放射性标记方面起着关键作用。本方法描绘了一个非常有用的模型来追踪肝脏中放射性标记代谢物的命运。
