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A biological method to evaluate bifunctional chelating agents to label antibodies with metallic radionuclides
Unlabelled:
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).
Methods:
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.
Results:
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.
Conclusion:
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.