title: Effect of carboxyl-group of D-glutamic acid or gamma-carboxy-D-glutamic acid as N-terminal amino acid of (111)in-diethylenetriaminepentaacetic acid-octreotide on accumulation of radioactivity in kidney.
abstract: To establish a strategy for developing (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA)-octreotide, a diagnostic radiopharmaceutical agent for tumors, with reduced non-specific renal radio-accumulation, the compounds having D-glutamic acid (Glu) or gamma-carboxy-D-glutamic acid (carboxy-Glu) as the N-terminal amino acid were examined for in vivo radio-distribution. Compounds carrying Glu and carboxy-Glu containing one and two negative charges, respectively, showed lower renal radio-accumulation than that carrying D-phenylalanine. It was revealed that the introduction of a negative charge reduces the renal radio-accumulation independently from the number of negative charges. The present result can be a clue for the development of (111)In-DTPA-octreotides with reduced the renal radio-accumulation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akizawa
authors.forename: Madoka
authors.initials: M
authors.lastname: Saito
authors.forename: Ikuko
authors.initials: I
authors.lastname: Tsukamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohkura
authors.forename: Takaya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Youji
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Mifune
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000737:chemistry*; D000818:Animals; D002021:Buffers; D002245:Carbon Dioxide / Q000737:chemistry*; D004355:Drug Stability; D018698:Glutamic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007205:Indium Radioisotopes; D007262:Infusions, Intravenous; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C442550:(111)indium-DTPA-D-phe octreoide; D002021:Buffers; D007205:Indium Radioisotopes; D010710:Phosphates; D019275:Radiopharmaceuticals; D002245:Carbon Dioxide; C041069:carboxyl radical; D018698:Glutamic Acid; D010649:Phenylalanine; D015055:1-Carboxyglutamic Acid; D004369:Pentetic Acid