TY - JOUR
T1 - Significance of 111In-DTPA chelate in renal radioactivity levels of 111In-DTPA-conjugated peptides
AU - Akizawa, Hiromichi
AU - Arano, Yasushi
AU - Mifune, Masaki
AU - Iwado, Akimasa
AU - Saito, Yutaka
AU - Uehara, Tomoya
AU - Ono, Masahiro
AU - Fujioka, Yasushi
AU - Ogawa, Kazuma
AU - Kiso, Yoshiaki
AU - Saji, Hideo
PY - 2001/6/21
Y1 - 2001/6/21
N2 - 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.
AB - 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.
KW - In-DTPA chelate
KW - In-DTPA-amino acid
KW - In-DTPA-peptide
KW - Renal radioactivity level
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U2 - 10.1016/S0969-8051(01)00207-4
DO - 10.1016/S0969-8051(01)00207-4
M3 - Article
C2 - 11395320
AN - SCOPUS:0035005266
VL - 28
SP - 459
EP - 468
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
SN - 0969-8051
IS - 4
ER -