Document Detail


Dual 19F/1H MR gene reporter molecules for in vivo detection of β-galactosidase.
MedLine Citation:
PMID:  22352428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased emphasis on personalized medicine and novel therapies requires the development of noninvasive strategies for assessing biochemistry in vivo. The detection of enzyme activity and gene expression in vivo is potentially important for the characterization of diseases and gene therapy. Magnetic resonance imaging (MRI) is a particularly promising tool, since it is noninvasive and has no associated radioactivity, yet penetrates deep tissue. We now demonstrate a novel class of dual (1)H/(19)F nuclear magnetic resonance (NMR) lacZ gene reporter molecule to specifically reveal enzyme activity in human tumor xenografts growing in mice. We report the design, synthesis, and characterization of six novel molecules and evaluation of the most effective reporter in mice in vivo. Substrates show a single (19)F NMR signal and exposure to β-galactosidase induces a large (19)F NMR chemical shift response. In the presence of ferric ions, the liberated aglycone generates intense proton MRI T(2) contrast. The dual modality approach allows both the detection of substrate and the imaging of product enhancing the confidence in enzyme detection.
Authors:
Jian-Xin Yu; Vikram D Kodibagkar; Rami R Hallac; Li Liu; Ralph P Mason
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-03-01
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  23     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-21     Completed Date:  2012-07-27     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  596-603     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Fluorine / chemistry*
Humans
Magnetic Resonance Imaging / methods*
Magnetic Resonance Spectroscopy
beta-Galactosidase / analysis*
Grant Support
ID/Acronym/Agency:
P30 CA142543/CA/NCI NIH HHS; P30 CA142543/CA/NCI NIH HHS; P30 CA142543-01/CA/NCI NIH HHS; P41 RR002584/RR/NCRR NIH HHS; P41 RR002584-22/RR/NCRR NIH HHS; P41-RR02584/RR/NCRR NIH HHS; R21 CA120774/CA/NCI NIH HHS; R21 CA120774/CA/NCI NIH HHS; R21 CA120774-01A1/CA/NCI NIH HHS; R21 CA120774-02/CA/NCI NIH HHS; U24 CA126608/CA/NCI NIH HHS; U24 CA126608/CA/NCI NIH HHS; U24 CA126608-03/CA/NCI NIH HHS; U24 CA126608-04/CA/NCI NIH HHS; U24 CA126608-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
284SYP0193/Fluorine; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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