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Title: Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications
Authors: Dai, L 
Jones, CM
Chan, WTK 
Pham, TA
Ling, X
Gale, EM
Rotile, NJ
Tai, WCS 
Anderson, CJ
Caravan, P
Law, GL 
Issue Date: 2018
Source: Nature communications, 2018, v. 9, no. 1, 857
Abstract: 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.
Publisher: Nature Publishing Group
Journal: Nature communications 
EISSN: 2041-1723
DOI: 10.1038/s41467-018-03315-8
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018
The following publication Dai, L., Jones, C. M., Chan, W. T. K., Pham, T. A., Ling, X., Gale, E. M., … Law, G. L. (2018). Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications. Nature Communications, 9(1), 857, 1-10 is available at https://dx.doi.org/10.1038/s41467-018-03315-8
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