MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch
Name
Jasanoff_MRI-based.pdf
Size
640.01 KB
Format
Adobe PDF
Checksum (MD5)
182e08981933387deac93937e61331a2
Author(s)
Westmeyer, Gil G.
Emer, Yelena
Lintelmann, Jutta
Jasanoff, Alan Pradip
Westmeyer, Gil Gregor
Date Issued
March 2014
Journal
Chemistry & Biology
Publisher
Elsevier
Citation
Westmeyer, Gil G., Yelena Emer, Jutta Lintelmann, and Alan Jasanoff. “MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch.” Chemistry & Biology 21, no. 3 (March 2014): 422–429.
Version
Author's final manuscript
Abstract
The ability to map patterns of gene expression noninvasively in living animals could have impact in many areas of biology. Reporter systems compatible with MRI could be particularly valuable, but existing strategies tend to lack sensitivity or specificity. Here we address the challenge of MRI-based gene mapping using the reporter enzyme secreted alkaline phosphatase (SEAP), in conjunction with a water-soluble metalloporphyrin contrast agent. SEAP cleaves the porphyrin into an insoluble product that accumulates at sites of enzyme expression and can be visualized by MRI and optical absorbance. The contrast mechanism functions in vitro, in brain slices, and in animals. The system also provides the possibility of readout both in the living animal and by postmortem histology, and it notably does not require intracellular delivery of the contrast agent. The solubility switch mechanism used to detect SEAP could be adapted for imaging of additional reporter enzymes or endogenous targets.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Nuclear Science and Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.chembiol.2014.01.012
