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

Metabolic studies of In-111-DTPA-labeled polypeptides and peptides showed that 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 different from metal-chelate adducts of other amino acids. Tn this study, to elucidate whether some biological characteristics of Met may accelerate the renal elimination rate of In-111-DTPA-adduct of Met into urine, In-111-DTPA-Met(1)-octreotide was synthesized and the renal handling of In-111-DTPA-Met was investigated using In-111-DTPA-L-Phe(1)-octreotide (Phe represents phenylalanine), 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 in 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 Phe, respectively, as the final radiometabolites at similar rates. These findings suggested that the long residence times of the radioactivity in tissues after administration of In-111-DTPA-labeled peptides and polypeptides would be attributed to inherent characteristics of In-111-DTPA chelate. (C) 2001 Elsevier Science Inc. All rights reserved.