期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 56, 期 6, 页码 2466-2477出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm301831f
关键词
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资金
- ENCITE EU-FP7 [HEALTH-F5-2008-201842]
- Regione Piemonte (Project PIIMDMT)
- MIUR [2009235JB7]
- Italian Consortium CIRCMSB
- Volkswagen Foundation [I/83 443]
Novel contrast agent based systems, which selectively visualize specific cells, e.g., neurons in the brain, would be of substantial importance for the fast developing field of molecular magnetic resonance imaging (MRI). We report here the synthesis and in vitro validation of a Gd(III)-based contrast agent designed to act as an MRI responsive probe for imaging the activity of the enzyme glutamic acid decarboxylase (GAD) present in neurons. Upon the action of the enzyme, the Gd(III) complex increases its hydration sphere and takes on a residual positive charge that promotes its binding to endogenous macromolecules. Both effects contribute in a synergic way to generate a marked relaxation enhancement, which directly reports enzyme activity and will allow activity detection of GAD positive cells in vitro and in vivo selectively.
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