MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch
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...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/99459 https://orcid.org/0000-0002-2834-6359 |
| _version_ | 1826194294456713216 |
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| author | Westmeyer, Gil G. Emer, Yelena Lintelmann, Jutta Jasanoff, Alan Pradip Westmeyer, Gil Gregor |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Westmeyer, Gil G. Emer, Yelena Lintelmann, Jutta Jasanoff, Alan Pradip Westmeyer, Gil Gregor |
| author_sort | Westmeyer, Gil G. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:53:50Z |
| format | Article |
| id | mit-1721.1/99459 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:53:50Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/994592023-02-26T02:08:46Z MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch Westmeyer, Gil G. Emer, Yelena Lintelmann, Jutta Jasanoff, Alan Pradip Westmeyer, Gil Gregor 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 Westmeyer, Gil G. Emer, Yelena Jasanoff, Alan Pradip 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. Raymond and Beverley Sackler Foundation National Institutes of Health (U.S.) (New Innovator Award Grant DP2-OD2441) MIT-Germany Seed Fund (Grant) 2015-10-27T12:01:17Z 2015-10-27T12:01:17Z 2014-03 2014-01 Article http://purl.org/eprint/type/JournalArticle 10745521 http://hdl.handle.net/1721.1/99459 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. https://orcid.org/0000-0002-2834-6359 en_US http://dx.doi.org/10.1016/j.chembiol.2014.01.012 Chemistry & Biology Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Westmeyer, Gil G. Emer, Yelena Lintelmann, Jutta Jasanoff, Alan Pradip Westmeyer, Gil Gregor MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title | MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title_full | MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title_fullStr | MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title_full_unstemmed | MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title_short | MRI-Based Detection of Alkaline Phosphatase Gene Reporter Activity Using a Porphyrin Solubility Switch |
| title_sort | mri based detection of alkaline phosphatase gene reporter activity using a porphyrin solubility switch |
| url | http://hdl.handle.net/1721.1/99459 https://orcid.org/0000-0002-2834-6359 |
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