RADIOLABELED METABOLITES OF PROTEINS PLAY A CRITICAL ROLE IN RADIOACTIVITY ELIMINATION FROM THE LIVER

被引:48
作者
ARANO, Y [1 ]
MUKAI, T [1 ]
AKIZAWA, H [1 ]
UEZONO, T [1 ]
MOTONARI, H [1 ]
WAKISAKA, K [1 ]
KAIRIYAMA, C [1 ]
YOKOYAMA, A [1 ]
机构
[1] KYOTO UNIV,FAC PHARMACEUT SCI,DEPT RADIOPHARMACEUT CHEM,SAKYO KU,KYOTO 60601,JAPAN
来源
NUCLEAR MEDICINE AND BIOLOGY | 1995年 / 22卷 / 05期
关键词
D O I
10.1016/0969-8051(95)00009-M
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
We have recently reported that the behavior of radiolabeled metabolites in the liver appears to be responsible for the hepatic radioactivity levels after administration of protein radiopharmaceuticals. To better understand the role played by radiolabeled metabolites in hepatic radioactivity levels, two benzyl-EDTA derivatives rendering different radiolabeled metabolites, 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA) and 1-[p-(5-maleimidopentyl)amino benzyl] ethylenediaminetetraacetic acid (ECMS-Bz-EDTA), were selected as bifunctional chelating agents (BCAs), and In-111 labeling of galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) was performed. Biodistribution of radioactivity in mice and subcellular distribution of radioactivity in hepatocytes were then compared. After accumulation in hepatic parenchymal cells, NGA-EMCS-Bz-EDTA-In-111 rendered a faster elimination rate of radioactivity from the liver than NGA-SCN-Bz-EDTA-In-111. Although each In-111-NMA exhibited a delayed elimination rate of radioactivity from the liver compared to the In-111-NGA counterpart, NMA-EMCS-Bz-EDTA-In-111 showed faster elimination rate of radioactivity than NMA-SCN-Bz-EDTA-In-111. Analyses of radioactivity excreted in feces and urine and remaining in the liver indicated that both BCAs rendered mono-amino acid adducts as the major radiolabeled metabolites (cysteine-EMCS-Bz-EDTA-In-111 and lysine-SCN-Bz-EDTA-In-111), which were generated in both cell types of the liver within 1 h postinjection. Subcellular distribution of radioactivity indicated that the radioactivity was copurified with lysosomes. These results demonstrate that although in vivo stability of radiometal chelates is essential, the biological properties of the radiolabeled metabolites generated after lysosomal proteolysis in hepatocytes play a critical role in radioactivity elimination from the liver.
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页码:555 / 564
页数:10
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