BIODISTRIBUTION AND METABOLISM OF TARGETED AND NONTARGETED PROTEIN-CHELATE-GADOLINIUM COMPLEXES - EVIDENCE FOR GADOLINIUM DISSOCIATION IN-VITRO AND IN-VIVO

被引：57

作者：

FRANANO, FN ^{[1
]}

EDWARDS, WB ^{[1
]}

WELCH, MJ ^{[1
]}

BRECHBIEL, MW ^{[1
]}

GANSOW, OA ^{[1
]}

DUNCAN, JR ^{[1
]}

机构：

[1] WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110

来源：

MAGNETIC RESONANCE IMAGING | 1995年 / 13卷 / 02期

关键词：

BIODISTRIBUTION; GADOLINIUM; GD-153; IN-111; GLYCOPROTEIN-CHELATE CONJUGATES;

D O I：

10.1016/0730-725X(94)00100-H

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：

The intracellular metabolism of receptor-targeted Gd-153-DTPA-glycoproteins was studied in vitro and in vivo. These agents bound to cell surface receptors, underwent receptor mediated endocytosis, and were rapidly degraded to a metabolite which co-migrated with a Gd-153-DTPA-lysine standard on thin layer chromatography. The rates of dissociation of (153)GD and In-111 from a glycoprotein-chelate conjugate were determined in vitro. Gadolinium readily dissociated, in a pH-sensitive manner, from glycoprotein-DTPA, and to a lesser degree glycoprotein-MX-DTPA. The biodistribution of targeted and blood pool (153)GD/In-111 labeled proteins also suggested that gadolinium dissociates from protein-DTPA and protein-MX-DTPA and their metabolites leading to an accumulation of gadolinium in bone. Metal-DTPA-glycoprotein agents targeted to cell surface receptors can still produce very high concentrations of radioactive or paramagnetic metals within the lysosome due to the high rate of accumulation afforded by receptor mediated endocytosis and the low release rate of metabolites such as metal-DTPA-lysine. However, the continued development of gadolinium based macromolecular agents will require improvements in bifunctional chelates.

引用

页码：201 / 214

页数：14

共 38 条

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