skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

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.

Authors:
 [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)
Publication Date:
Research Org.:
Univ. of Pittsburgh, Pittsburgh, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1511482
Grant/Contract Number:  
SC0008833
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Dai, Lixiong, Jones, Chloe M., Chan, Wesley Ting Kwok, Pham, Tiffany A., Ling, Xiaoxi, Gale, Eric M., Rotile, Nicholas J., Tai, William Chi-Shing, Anderson, Carolyn J., Caravan, Peter, and Law, Ga -Lai. Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications. United States: N. p., 2018. Web. doi:10.1038/s41467-018-03315-8.
Dai, Lixiong, Jones, Chloe M., Chan, Wesley Ting Kwok, Pham, Tiffany A., Ling, Xiaoxi, Gale, Eric M., Rotile, Nicholas J., Tai, William Chi-Shing, Anderson, Carolyn J., Caravan, Peter, & Law, Ga -Lai. Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications. United States. doi:10.1038/s41467-018-03315-8.
Dai, Lixiong, Jones, Chloe M., Chan, Wesley Ting Kwok, Pham, Tiffany A., Ling, Xiaoxi, Gale, Eric M., Rotile, Nicholas J., Tai, William Chi-Shing, Anderson, Carolyn J., Caravan, Peter, and Law, Ga -Lai. Tue . "Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications". United States. doi:10.1038/s41467-018-03315-8. https://www.osti.gov/servlets/purl/1511482.
@article{osti_1511482,
title = {Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications},
author = {Dai, Lixiong and Jones, Chloe M. and Chan, Wesley Ting Kwok and Pham, Tiffany A. and Ling, Xiaoxi and Gale, Eric M. and Rotile, Nicholas J. and Tai, William Chi-Shing and Anderson, Carolyn J. and Caravan, Peter and Law, Ga -Lai},
abstractNote = {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.},
doi = {10.1038/s41467-018-03315-8},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

Save / Share: