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

Metabolic studies of ¹¹¹In-DTPA-labeled polypeptides and peptides showed that the radiolabeled (poly)peptides generated ¹¹¹In-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. In this study, to elucidate whether some biological characteristics of Met may accelerate the renal elimination rate of ¹¹¹In-DTPA-adduct of Met into urine, ¹¹¹In-DTPA-Met¹-octreotide was synthesized and the renal handling of ¹¹¹In-DTPA-Met was investigated using ¹¹¹In-DTPA-L-Phe¹-octreotide (Phe represents phenylalanine), which was reported previously, as a reference. Both ¹¹¹In-DTPA-conjugated octreotide analogs were stable against 3-h incubation in murine serum at 37°C. Both ¹¹¹In-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 ¹¹¹In-DTPA-Met¹-octreotide and ¹¹¹In-DTPA-L-Phe¹-octreotide generated ¹¹¹In-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 ¹¹¹In-DTPA-labeled peptides and polypeptides would be attributed to inherent characteristics of ¹¹¹In-DTPA chelate.