title: Significance of (111)In-DTPA chelate in renal radioactivity levels of (111)In-DTPA-conjugated peptides.
abstract: Metabolic studies of (111)In-DTPA-labeled polypeptides and peptides showed that the radiolabeled (poly)peptides generated (111)In-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 (111)In-DTPA-adduct of Met into urine, (111)In-DTPA-Met(1)-octreotide was synthesized and the renal handling of (111)In-DTPA-Met was investigated using (111)In-DTPA-L-Phe(1)-octreotide (Phe represents phenylalanine), which was reported previously, as a reference. Both (111)In-DTPA-conjugated octreotide analogs were stable against 3-h incubation in murine serum at 37 degrees C. Both (111)In-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 (111)In-DTPA-Met(1)-octreotide and (111)In-DTPA-L-Phe(1)-octreotide generated (111)In-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 (111)In-DTPA-labeled peptides and polypeptides would be attributed to inherent characteristics of (111)In-DTPA chelate.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, 700-8530, Tsushima-naka, Okayama, Japan. aki@pheasant.pharm.okayama-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Akizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Arano
authors.forename: M
authors.initials: M
authors.lastname: Mifune
authors.forename: A
authors.initials: A
authors.lastname: Iwado
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Uehara
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kiso
authors.forename: H
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D007202:Indicators and Reagents; D007668:Kidney / Q000000981:diagnostic imaging*; D008297:Male; D008715:Methionine; D051379:Mice; D015282:Octreotide; D004369:Pentetic Acid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D007202:Indicators and Reagents; D010455:Peptides; D019275:Radiopharmaceuticals; D004369:Pentetic Acid; D008715:Methionine; D015282:Octreotide