Effect of carboxylation of N-terminal phenylalanine of (111)in-DTPA (diethylenetriaminepentaacetic acid)-octreotide on accumulation of radioactivity in kidney.
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.
Akizawa
Hiromichi
H
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Okayama 700-8530, Japan. aki@pheasant.pharm.okayama-u.ac.jp
Takimoto
Hirokazu
H
Saito
Madoka
M
Iwado
Akimasa
A
Mifune
Masaki
M
Saito
Yutaka
Y
Uehara
Tomoya
T
Arano
Yasushi
Y
Mukai
Takahiro
T
Hanaoka
Hirofumi
H
Saji
Hideo
H
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
C442550:(111)indium-DTPA-D-phe octreoide; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D010649:Phenylalanine; D004369:Pentetic Acid