Metabolism of receptor targeted 111In-DTPA-glycoproteins: identification of 111In-DTPA-epsilon-lysine as the primary metabolic and excretory product.
The hepatic and renal retention of indium-111 (111In) from 111In-labeled polypeptides has been the subject of many investigations. Because the lysosome is a common intracellular destination for the degradation of polypeptides, we studied the lysosomal metabolism of 111In-DTPA-labeled glycoproteins targeted to cell surface receptors in vitro and in vivo. We found that 111In-DTPA-glycoproteins were degraded to 111In-DTPA-epsilon-lysine, which was slowly released from cells and recovered intact in urine and feces. These results suggest a mechanism for 111In retention at target and non-target sites.
Franano
F N
FN
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Edwards
W B
WB
Welch
M J
MJ
Duncan
J R
JR
D000818:Animals; D002460:Cell Line; D005243:Feces / Q000737:chemistry; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D051379:Mice; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D006023:Glycoproteins; C107865:indium DTPA-epsilon-lysine; D004369:Pentetic Acid; D008239:Lysine