具有优化生物分布特性的新型99mTc标记神经降压素类似物。

Novel 99mTc-labeled neurotensin analogues with optimized biodistribution properties.

作者信息

Maes Veronique, Garcia-Garayoa Elisa, Bläuenstein Peter, Tourwé Dirk

机构信息

Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.

出版信息

J Med Chem. 2006 Mar 9;49(5):1833-6. doi: 10.1021/jm051172f.

DOI:10.1021/jm051172f

PMID:16509599

Abstract

Two new 99mTc-labeled neurotensin(8-13) analogues containing the retro-N(alpha)-carboxymethyl-histidine ((N(alpha)His)Ac) chelator were synthesized as potential radiopharmaceuticals for visualization of pancreatic carcinoma. To improve the pharmacokinetic properties, (N(alpha)His)Ac-Arg-NMeArg-Pro-Tyr-Tle-Leu (NT-XII), which is metabolically stabilized at two positions, was further modified. Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) was introduced to obtain a more hydrophilic peptide (NT-XVIII), or Tyr11 was replaced by 2,6-dimethyltyrosine (Dmt) resulting in a triple-stabilized NT(8-13) analogue (NT-XIX). The latter has the best biodistribution profile.

摘要

合成了两种新的含有反向N(α)-羧甲基组氨酸((N(α)His)Ac)螯合剂的99mTc标记的神经降压素(8-13)类似物，作为可视化胰腺癌的潜在放射性药物。为改善药代动力学性质，对在两个位置代谢稳定的(N(α)His)Ac-Arg-NMeArg-Pro-Tyr-Tle-Leu(NT-XII)进行了进一步修饰。引入莽草酸(3,4,5-三羟基-1-环己烯-1-羧酸)以获得更亲水的肽(NT-XVIII)，或者用2,6-二甲基酪氨酸(Dmt)取代Tyr11，得到一种三重稳定的NT(8-13)类似物(NT-XIX)。后者具有最佳的生物分布情况。