Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, 02129, United States.
Nat Commun. 2018 Feb 27;9(1):857. doi: 10.1038/s41467-018-03315-8.
Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA]. These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.
尽管已经在临床上得到了应用，但人们越来越需要更安全、惰性更低的基于钆的造影剂，以及与放射性金属快速反应的螯合剂。在这里，我们报告了一系列手性 DOTA 螯合剂及其相应的金属配合物的合成，并揭示了超越母体 DOTA 化合物的性质。我们在四氮杂环周围引入了对称的手性取代基，赋予 DOTA 腔增强的刚性，从而能够控制镧系元素配合物的立体异构体范围。结果表明，与 [GdDOTA] 相比，这些 Gd 手性 DOTA 配合物的 Gd 释放惰性要高出几个数量级。这些化合物在高场成像的最佳范围内还表现出非常快的水交换速率。与 (Cu-64/Lu-177) 的放射性标记研究也证明了更快的标记特性。这些手性 DOTA 螯合剂是开发稳定、高弛豫率造影剂以及用于成像和/或治疗的放射性金属配合物的替代通用平台。
