Synthesis and evaluation of a novel bifunctional ligand 3o-C-NETA for Yttrium-90 and Lutetium-177

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-02-11 DOI:10.1016/j.bmcl.2025.130136

Hua Xu, Pengfei Dong, Haixing Wang, Inseok Sin, Chi Soo Kang, Siyuan Ren, Xiang Sun, Hyun-Soon Chong

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Abstract

A bifunctional ligand is an essential component for targeted cancer therapy using cytotoxic radionuclides. We report the synthesis and evaluation of a novel bifunctional ligand, 3o-C-NETA, designed for labeling a bioactive small molecule or an antibody with β-particle emitting radionuclides ⁹⁰Y and ¹⁷⁷Lu. 3o-C-NETA is an octadentate chelating agent and contains both a macrocyclic backbone (1,4,7-triazacyclononane, TACN) and pendant donor groups. 3o-C-NETA was efficiently synthesized via the regiospecific ring opening of a functionalized aziridinium ion with tert-Butyl protected NODA (1,4,7-triazacyclononane-1,4-diacetic acid) and evaluated for radiolabeling kinetics and in vitro complex stability with ⁹⁰Y and ¹⁷⁷Lu. The new bifunctional ligand (3o-C-NETA) rapidly bound to ⁹⁰Y or ¹⁷⁷Lu, and the corresponding ⁹⁰Y- or ¹⁷⁷Lu-labeled 3o-C-NETA remained stable in human serum for two weeks.

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新型钇-90和镥-177双功能配体30 - c - neta的合成与评价。

双功能配体是使用细胞毒性放射性核素靶向癌症治疗的重要组成部分。我们报道了一种新的双功能配体30 - c - neta的合成和评价，该配体设计用于标记具有生物活性的小分子或具有发射放射性核素90Y和177Lu的β-颗粒的抗体。30 - c - neta是一种十八齿酸螯合剂，含有大环主链（1,4,7-三氮杂环壬烷，TACN）和垂链供体基团。用叔丁基保护的NODA（1,4,7-三氮环壬烷-1,4-二乙酸）通过功能化氮铱离子的区域特异性开环高效合成了30 - c - neta，并对其与90Y和177Lu的放射性标记动力学和体外配合物稳定性进行了评价。新的双功能配体（30 - c - neta）快速结合90Y或177Lu，相应的90Y或177Lu标记的30 - c - neta在人血清中保持稳定两周。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.