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

Lixiong Dai, Chloe M. Jones, Wesley Ting Kwok Chan, Tiffany A. Pham, Xiaoxi Ling, Eric M. Gale, Nicholas J. Rotile, Chi Shing Tai, Carolyn J. Anderson, Peter Caravan, Ga Lai Law

Research output: Journal article publicationJournal articleAcademic researchpeer-review

43 Citations (Scopus)


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.
Original languageEnglish
Article number857
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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