Role of transchelation in the uptake of 99mTc-MAb in liver and kidney.
High radioactivity in liver and kidney after administration of 99mTc-labeled antibodies is a major detriment to the use of radiolabeled antibodies for diagnosis and therapy. In the present study, the uptake mechanism of radioactivity by liver and kidney involving 99mTc moiety was investigated. The data of in vitro and in vivo thiol transchelation studies, biodistribution alteration of 99mTc-MAb after specific modulation of endogenous thiol containing compounds, and the finding of 99mTc-labeled cysteine and GSH in bile, urine and kidney after administration of 99mTc-MAb demonstrated that transchelation by thiols (cysteine and GSH) played an important role in the localization of radiotracer from 99mTc MAb in normal tissues such as liver and kidney.
Xue
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LY
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Noujaim
A A
AA
Sykes
T R
TR
Woo
T K
TK
Wang
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XB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000493:pharmacokinetics*; D002614:Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry; D003545:Cysteine / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000008:administration & dosage* / Q000737:chemistry; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D013667:Technetium / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D013667:Technetium; D008668:Metallothionein; D005978:Glutathione; D003545:Cysteine