Effect of carboxylation of N-terminal phenylalanine of (111)in-DTPA (diethylenetriaminepentaacetic acid)-octreotide on accumulation of radioactivity in kidney.
Effect of carboxylation of N-terminal phenylalanine of (111)in-DTPA (diethylenetriaminepentaacetic acid)-octreotide on accumulation of radioactivity in kidney.
复制标题
(111)in-DTPA（二亚乙基三胺五乙酸）-奥曲肽 N 端苯丙氨酸羧化对肾脏放射性蓄积的影响。
DOI：
10.1248/bpb.27.271
复制
发表时间：
2004
影响因子：
2
通讯作者：
H. Saji
中科院分区：
文献类型：
--
作者：
H. Akizawa;H. Takimoto;Madoka Saito;A. Iwado;M. Mifune;Yutaka Saito;T. Uehara;Y. Arano;T. Mukai;H. Hanaoka;H. Saji
为了减少已知放射性药剂的放射性在肾中的蓄积，即，（111）合成了对羧基苯丙氨酸取代D-Phe（1）的In-DTPA-D-Phe（1）-奥曲肽衍生物。所得的具有羧基取代的L-Phe的化合物（1）的生物分布研究显示，肾蓄积显著低于具有未取代的L-Phe的对照化合物（1），表明奥曲肽的N-末端氨基酸上存在负电荷对减少肾蓄积是有效的。这种效应可能是由于肾刷状缘膜的亲脂性降低以及负电荷产生的排斥力所致。
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.