Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications

Nature Communications
Lixiong DaiGa-Lai Law

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.

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Citations

Apr 4, 2019·Chemical Communications : Chem Comm·Thomas MüntenerDaniel Häussinger
Mar 17, 2020·Chemical Society Reviews·Xueli ZhaoXiaoyuan Chen
May 7, 2020·Chemical Communications : Chem Comm·Meng YuEmily L Que
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Mar 11, 2021·Inorganic Chemistry·Lixiong DaiGa-Lai Law
Aug 17, 2021·Organic & Biomolecular Chemistry·Rosaria SchettiniFrancesco De Riccardis
Oct 24, 2018·Chemical Reviews·Jessica WahsnerPeter Caravan
Nov 7, 2019·Inorganic Chemistry·Lea Gundorff Nielsen, Thomas Just Sørensen
Aug 29, 2020·Inorganic Chemistry·Eunji LeeYoichi Habata

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Methods Mentioned

BETA
NMR
X-ray
electron paramagnetic resonance

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