NDLI: A copper -activated magnetic resonance imaging contrast agent with improved turn-on relaxivity response and anion compatibility

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Baker, Suzanne L. Chang, Christopher J. Gianolio, Eliana Que, Emily L. Aime, Silvio
Description	Author Affiliation: Que EL ( Department of Chemistry, University of California, Berkeley, CA 94720, USA.)
Abstract	We present the synthesis and characterization of Copper-Gad-7 (CG7), a new copper -activated magnetic resonance imaging (MRI) contrast agent that possesses a Gd $^{3+}$ –DO3A scaffold with an appended thioether-rich receptor for copper recognition. Installation of additional carboxylate groups on the periphery of the CG scaffold affords a practical strategy to increase the absolute relaxivity of these types of copper -responsive MRI sensors as well as reduce their sensitivity to biologically abundant anions. Due in large part to restricted access of inner-sphere water molecules to the paramagnetic Gd $^{3+}$ core, in the absence of copper ions, CG7 exhibits a relatively low relaxivity value of r $_{1}$ = 2.6 $mM^{−1}$ $s^{−1};$ addition of Cu $^{+}$ triggers a 340% enhancement in relaxivity to $r_{1}$ = 11.4 $mM^{−1}$ $s^{−1}.$ For comparison, the relaxivity of the analogous CG2 sensor without peripheral carboxylates increases from r $_{1}$ = 1.5 to 6.9 $mM^{−1}$ $s^{−1}$ upon Cu $^{+}$ binding. CG7 features high selectivity for Cu $^{+}$ over a range of biologically relevant metal ions, including the cellular abundant alkali and alkaline earth cations and d-block ions Zn $^{2+}$ and Cu $^{2+}$ . Moreover, the Cu $^{+}$ -response of the CG7 sensor is not significantly affected by bicarbonate , phosphate , citrate , and lactate anions at cellular levels. $^{17}O$ NMR dysprosium -induced shift (DIS) and nuclear magnetic relaxation dispersion (NMRD) experiments suggest that the origin of the improved anion compatibility of CG7 is a reduced q modulation compared to previous members of the CG family, and $T_{1}-weighted$ phantom images confirm that CG7 can monitor changes in copper levels by MRI at clinically relevant field strengths.
ISSN	14779226
Issue Number	2
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2010-01-14
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Anions Chemistry Contrast Media Copper Magnetic Resonance Imaging Organometallic Compounds Chemical Synthesis Dysprosium Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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