METABOLISM OF RECEPTOR TARGETED IN-111-DTPA-GLYCOPROTEINS - IDENTIFICATION OF IN-111-DTPA-EPSILON-LYSINE AS THE PRIMARY METABOLIC AND EXCRETORY PRODUCT

The hepatic and renal retention of indium-111 (In-111) from In-111-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 In-111-DTPA-labeled glycoproteins targeted to cell surface receptors in vitro and in vivo. We found that In-111-DTPA-glycoproteins were degraded to In-111-DTPA-epsilon-lysine, which was slowly released from cells and recovered intact in urine and feces. These results suggest a mechanism for In-111 retention at target and non-target sites.