title: Effect of carboxylation of N-terminal phenylalanine of (111)in-DTPA (diethylenetriaminepentaacetic acid)-octreotide on accumulation of radioactivity in kidney.
abstract: For purpose of reducing renal accumulation of radioactivity of a known radiopharmaceutical agent, i.e., (111)In-DTPA (diethylenetriaminepentaacetic acid)-D-Phe(1)-octreotide, a derivative in which p-carboxy-L-phenylalanine is substituted for D-Phe(1) was synthesized. Biodistribution study of the resultant compound having carboxy-substituted L-Phe(1) revealed that the renal accumulation was significantly lower than that of control compound having unsubstituted L-Phe(1), demonstrating that the presence of negative charge on the N-terminal amino acid of octreotide is effective to reduce the renal accumulation. This effect can be attributed to the reduction of lipophilicity and also the repulsive force arisen from the negative charge of renal brush border membrane.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Okayama 700-8530, Japan. aki@pheasant.pharm.okayama-u.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akizawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takimoto
authors.forename: Madoka
authors.initials: M
authors.lastname: Saito
authors.forename: Akimasa
authors.initials: A
authors.lastname: Iwado
authors.forename: Masaki
authors.initials: M
authors.lastname: Mifune
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Saito
authors.forename: Tomoya
authors.initials: T
authors.lastname: Uehara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D004355:Drug Stability; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010649:Phenylalanine / Q000737:chemistry*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C442550:(111)indium-DTPA-D-phe octreoide; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D010649:Phenylalanine; D004369:Pentetic Acid