Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 135, Issue 40, Pages 14904-14907Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja406738y
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Funding
- National Institutes of Health [CA-115531, EB-02584, EB-00482]
- Robert A. Welch Foundation [AT-584]
- Cancer Prevention Research Institute of Texas (CPRIT) [RP100146]
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A novel approach for the design of responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents has been developed where the signal is turned on by altering the longitudinal relaxation time (T-1) of bulk water protons. To demonstrate this approach, a model Eu(DOTA-tetraamide) complex (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) containing two nitroxide free radical units was synthesized. The nitroxide groups substantially shortened the T-1 of the bulk water protons which, in turn, resulted in quenching of the CEST signal. Reduction of paramagnetic nitroxide moieties to a diamagnetic species resulted in the appearance of CEST. The modulation of CEST by T, relaxation provides a new platform for designing biologically responsive MRI agents.
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