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

Journal Article · · Nature Communications
 [1];  [2];  [1];  [3]; ORCiD logo [3]; ORCiD logo [2];  [2];  [1]; ORCiD logo [3];  [2]; ORCiD logo [1]
  1. The Hong Kong Polytechnic Univ., Hong Kong (China)
  2. Massachusetts General Hospital and Harvard Medical School, Charlestown, MA (United States)
  3. Univ. of Pittsburgh, Pittsburgh, PA (United States)
+ Show Author Affiliations

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.

Research Organization:
Univ. of Pittsburgh, PA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0008833
OSTI ID:
1511482
Journal Information:
Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 53 works
Citation information provided by
Web of Science

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Cited By (9)

A Sterically Overcrowded, Isopropyl‐Substituted, Lanthanide‐Chelating Tag for Protein Pseudocontact Shift NMR Spectroscopy: Synthesis of its Macrocyclic Scaffold and Benchmarking on Ubiquitin S57 C and hCA II S166 C journal August 2019
Effect of Ligand Chirality and Hyperconjugation on the Thermodynamic Stability of a Tris(aquated) Gd III Complex: Synthesis, Characterization, and T 1 -Weighted Phantom MR Image Study: Effect of Ligand Chirality and Hyperconjugation on the Thermodynamic Stability of a Tris(aquated) GdIII Complex: Synthesis, Characterization, and T1-W journal May 2019
The Use of the Macrocyclic Chelator DOTA in Radiochemical Separations: The Use of the Macrocyclic Chelator DOTA in Radiochemical Separations journal November 2019
A Bishydrated, Eight–Coordinate Gd(III) Complex with Very Fast Water Exchange: Synthesis, Characterization, and Phantom MR Imaging journal July 2018
Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents journal March 2019
Synthesis of chiral nine and twelve-membered cyclic polyamines from natural building blocks journal January 2019
The use of the macrocyclic chelator DOTA in radiochemical separations text January 2020
Synthesis of chiral nine and twelve-membered cyclic polyamines from natural building blocks text January 2019
A Sterically Overcrowded, Isopropyl-Substituted, Lanthanide-Chelating Tag for Protein Pseudocontact Shift NMR Spectroscopy: Synthesis of its Macrocyclic Scaffold and Benchmarking on Ubiquitin S57 C and hCA II S166 C text January 2019

Linked Research (6)

Figures / Tables (10)

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