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S‐Gal®, A novel 1 H MRI reporter for β‐galactosidase
Author(s) -
Cui Weina,
Liu Li,
Kodibagkar Vikram D.,
Mason Ralph P.
Publication year - 2010
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.22400
Subject(s) - in vivo , chemistry , enzyme , reporter gene , in vitro , stain , beta (programming language) , enzyme assay , ferric , beta galactosidase , microbiology and biotechnology , gene expression , nuclear magnetic resonance , gene , biochemistry , staining , biology , genetics , physics , organic chemistry , computer science , programming language
Reporter genes and associated enzyme activity are becoming increasingly significant for research in vivo. The lacZ gene and β‐galactosidase (β‐gal) expression have long been exploited as reporters of biologic manipulation at the molecular level, and a noninvasive detection strategy based on proton MRI is particularly attractive. 3,4‐Cyclohexenoesculetin β‐ D ‐galactopyranoside (S‐Gal®) is a commercial histologic stain, which forms a black precipitate in the presence of β‐gal and ferric ions, suggesting potential detectability by MRI. Generation of the precipitate is now shown to cause strong T 2 * relaxation, revealing β‐gal activity. A series of tests with the enzyme in vitro and with tumor cells shows that this approach can be used as an assay for β‐gal activity. Proof of principle is shown in human breast tumor xenografts in mice. Upon direct injection of a mixture of 3,4‐cyclohexenoesculetin β‐ D ‐galactopyranoside and ferric ammonium citrate, intense contrast was observed immediately in MCF7‐ lacZ tumors, but not in wild‐type tumors. 3,4‐Cyclohexenoesculetin β‐ D ‐galactopyranoside activation in combination with ferric ions introduces a novel approach for assaying enzyme activity by MRI in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.