Significance of In-111-DTPA chelate in renal radioactivity levels of In-111-DTPA-conjugated peptides

Metabolic studies of In-111-DTPA-labeled polypeptides and peptides showed t hat the radiolabeled (poly)peptides generated In-111-DTPA-adducts of amino acid that possess long residence times in the lysosomal compartment of the tissues where (poly)peptides accumulated. However, a recent study suggested that metal-chelate-methionine (Met) might possess in vivo behaviors differ ent from metal-chelate adducts of other amino acids. Tn this study, to eluc idate whether some biological characteristics of Met may accelerate the ren al elimination rate of In-111-DTPA-adduct of Met into urine, In-111-DTPA-Me t(1)-octreotide was synthesized and the renal handling of In-111-DTPA-Met w as investigated using In-111-DTPA-L-Phe(1)-octreotide (Phe represents pheny lalanine), which was reported previously, as a reference. Both In-111-DTPA- conjugated octreotide analogs were stable against 3-h incubation in murine serum at 37 degreesC. Both In-111-DTPA-octreotide analogs also showed rapid clearance of the radioactivity from the blood and similar accumulation of the radioactivity in the kidney. No significant differences were observed i n the renal radioactivity levels from 10 min to 24 h postinjection between the two. Metabolic studies indicated that In-111-DTPA-Met(1)-octreotide and In-111-DTPA-L-Phe(1)-octreotide generated In-111-DTPA-adducts of Met and P he, respectively, as the final radiometabolites at similar rates. These fin dings suggested that the long residence times of the radioactivity in tissu es after administration of In-111-DTPA-labeled peptides and polypeptides wo uld be attributed to inherent characteristics of In-111-DTPA chelate. (C) 2 001 Elsevier Science Inc. All rights reserved.