Advancing Chelation Strategies for Large Metal Ions for Nuclear Medicine Applications.
Advancing Chelation Strategies for Large Metal Ions for Nuclear Medicine Applications.
复制标题
DOI：
10.1021/acs.accounts.2c00003
复制
发表时间：
2022-03-15
影响因子：
18.3
通讯作者：
Wilson, Justin J.
中科院分区：
文献类型：
--
作者：
Hu, Aohan;Wilson, Justin J.
核医学利用各种元素的放射性同位素，其中很大一部分是金属，用于疾病的诊断和治疗。为了将金属离子的放射性同位素或放射性金属最佳地用于这些应用，需要与它们有效地形成化学上和动力学上稳定的络合物的螯合剂。螯合剂还起到附着于定位病理组织的生物靶向载体的作用。迄今为止，已经建立了许多适合于小放射性金属的螯合剂，但是对于大放射性金属有效的螯合剂明显不太常见。本文介绍了近年来我们和其他人在大放射性金属螯合配体方面的进展，以及在核医学中的应用。首先，我们讨论和分析的螯合剂macropa，一个大环配体，含有18-冠-6骨干和两个吡啶羧酸悬垂臂，与大的金属离子在核医学的背景下的配位化学。这种配体以其不寻常的反向尺寸选择性而闻名，或者优先结合大而不是小的金属离子。介绍了大放射性金属225 Ac 3+、132/135 La 3+、131 Ba 2+、223 Ra 2+、213 Bi 3+对巨噬细胞的放射性标记特性以及相关的体内研究。本文还简要介绍了大环核中含有不同侧链给体或刚性基团的大环芳烃衍生物的研究进展。接下来，总结了通过共价缀合至生物靶向载体将macropa转化为放射性药剂的努力。在这次讨论中，两种不同类型的双功能类似物的macropa在文献中报道，macropa-NCS和MCP-点击，提出。他们的实施在不同的放射性药物制剂进行了讨论。本发明提供了含有与小分子靶向载体或大分子抗体连接的macropa的生物缀合物。这些结构的体外和体内评价进行了讨论。最后，描述了具有双重尺寸选择性的螯合剂。这类配体对大金属离子和小金属离子都表现出良好的亲和力。这种性质对于需要同时螯合具有互补治疗和诊断性质的大和小放射性金属的核医学应用是有价值的。最近，我们报道了一个18元大环配体称为macrodipa，达到这种选择性模式。这种螯合剂，它的第二代类似物py-macrodipa，和它们的应用螯合的药物相关的大135 La 3+，225 Ac 3+，213 Bi 3+和小44 Sc 3+离子也被提出。这些放射性金属的研究表明，py-macrodipa可以有效地放射性标记和稳定地保留小和大的放射性金属。总的来说，这个帐户使创新的配体设计方法，采用新出现的放射性金属离子与不寻常的配位化学性质的情况下。
Nuclear medicine leverages radioisotopes of a wide range of elements, a significant portion of which are metals, for the diagnosis and treatment of disease. To optimally use the radioisotopes of the metal ions, or radiometals, for these applications, a chelator that efficiently forms thermodynamically and kinetically stable complexes with them is required. The chelator also serves a role of attaching to a biological targeting vector that locates pathological tissues. Numerous chelators suitable for small radiometals have been established to date, but chelators that work well for large radiometals are significantly less common. In this Account, we describe recent progress by us and others in the advancement of ligands for large radiometals chelation with arising applications in nuclear medicine. First, we discuss and analyze the coordination chemistry of the chelator macropa, a macrocyclic ligand that contains the 18-crown-6 backbone and two picolinate pendent arms, with large metal ions in the context of nuclear medicine. This ligand is known for its unusual reverse size selectivity, or preference for binding large over small metal ions. The radiolabeling properties of macropa with the large radiometals 225Ac3+, 132/135La3+, 131Ba2+, 223Ra2+, 213Bi3+, and the related in vivo investigations are described. The development of macropa derivatives containing different pendent donors or rigidifying groups in the macrocyclic core is also briefly reviewed. Next, efforts towards transforming macropa into a radiopharmaceutical agent via covalent conjugation to biological targeting vectors are summarized. In this discussion, two different types of bifunctional analogues of macropa reported in the literature, macropa-NCS and mcp-click, are presented. Their implementation in different radiopharmaceutical agents is discussed. Bioconjugates containing macropa attached to small-molecule targeting vectors or macromolecular antibodies are presented. The in vitro and in vivo evaluation of these constructs is also discussed. Lastly, chelators with a dual size selectivity are described. This class of ligands exhibits good affinities to both the large and small metal ions. This property is valuable for nuclear medicine applications that require the simultaneous chelation of both large and small radiometals with complementary therapeutic and diagnostic properties. Recently, we reported an 18-membered macrocyclic ligand called macrodipa that attains this selectivity pattern. This chelator, its second generation analogue py-macrodipa, and their applications for chelating the medicinally relevant large 135La3+, 225Ac3+, 213Bi3+ and small 44Sc3+ ions are also presented. Studies with these radiometals show that py-macrodipa can effectively radiolabel and stably retain both small and large radiometals. Overall, this Account makes the case for innovative ligand design approaches to employ novel arising radiometal ions with unusual coordination chemistry properties.
登录
查看更多内容
DOI：
10.3390/molecules26010004
发表时间：
2020-12-22
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Bell MM;Gutsche NT;King AP;Baidoo KE;Kelada OJ;Choyke PL;Escorcia FE
通讯作者：
Escorcia FE
影响因子：
4.6
作者：
Ferreiros-Martinez, Raquel;Esteban-Gomez, David;Rodriguez-Blas, Teresa
通讯作者：
Rodriguez-Blas, Teresa
影响因子：
4.6
作者：
Fiszbein DJ;Brown V;Thiele NA;Woods JJ;Wharton L;MacMillan SN;Radchenko V;Ramogida CF;Wilson JJ
通讯作者：
Wilson JJ
影响因子：
4.6
作者：
Aluicio-Sarduy, Eduardo;Hernandez, Reinier;Engle, Jonathan W.
通讯作者：
Engle, Jonathan W.
影响因子：
3.4
作者：
Frantellizzi, Viviana;Cosma, Laura;De Vincentis, Giuseppe
通讯作者：
De Vincentis, Giuseppe