Studies on metabolism of directly labeled 99mTc-antibody in mice.
The elucidation on the metabolic products of the 99mTc-antibody conjugates may provide insights and approaches that would reduce the undesirable deposition of radioactive species in normal tissues. In this investigation, the radiolabeled species in blood, urine, bile and extracts of liver and kidney obtained at different times after the injection of a model antibody, 99mTc-MAb170, into mice were analyzed with various chromatographic methods. Ninety-nine to 100% of the radioactivity in serum was associated with intact MAb170. The radioactivity in liver homogenate extract was strictly protein-bound to either intact MAb or low molecular weight species (LMW). In kidney extracts, the majority of the radioactivity was protein bound 99mTc, with less than 8% of the activity being non-protein bound 99mTc. Multiple 99mTc-containing protein and non-protein species were found in urine and bile. Evidence supporting the presence of 99mTc-cysteine and 99mTc-glutathione in bile, kidney and urine was also obtained. No evidence for the in vivo formation of 99mTc-pertechnetate in mouse blood, liver, kidney, bile and urine was observed.
Xue
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LY
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Noujaim
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AA
Sykes
T R
TR
Woo
T K
TK
Peng
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D051379:Mice; D008807:Mice, Inbred BALB C; D016719:Radioimmunodetection; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D013667:Technetium