ArticleActa oncologica (Stockholm, Sweden)2008
Non-invasive molecular and functional imaging of cytosine deaminase and uracil phosphoribosyltransferase fused with red fluorescence protein.
Article in Acta oncologica (Stockholm, Sweden), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Clostridium Bacteria: Harnessing Tumour Necrosis for Targeted Gene Delivery.Molecular diagnosis & therapy · 2024Article
- Luciferase-based reporting of suicide gene activity in murine mesenchymal stem cells.PloS one · 2019Article
- Cytosine deaminase as a negative selectable marker for the microalgal chloroplast: a strategy for the isolation of nuclear mutations that affect chloroplast gene expression.The Plant journal : for cell and molecular biology · 2014Article
- A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions.Cancer gene therapy · 2013Article
- Hypoxia targeted bifunctional suicide gene expression enhances radiotherapy in vitro and in vivo.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2012Article
- Prodrug enzymes and their applications in image-guided therapy of cancer: tracking prodrug enzymes to minimize collateral damage.Drug delivery and translational research · 2012Article
- Magnetic resonance reporter gene imaging.Theranostics · 2012Article
- Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter.Gene therapy · 2011Article
- Expression of the bifunctional suicide gene CDUPRT increases radiosensitization and bystander effect of 5-FC in prostate cancer cells.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2009Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
introductionIncreased expression of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) may improve the antitumoral effect of 5-fluorouracil (5-FU) and 5-fluorocytosine (5-FC), and thereby enhance the potential of gene-directed enzyme prodrug therapy. For the applicability of gene-directed enzyme prodrug therapy in a clinical setting, it is essential to be able to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using magnetic resonance spectroscopy and optical imaging to measure non-invasively CD and UPRT expression and function. MATERIALS AND
methodsExpression vectors of CD or CD/UPRT fused to monomeric DsRed (mDsRed) were constructed and rat prostate carcinoma (R3327-AT) cell lines stably expressing either CD/mDsRed or CD/UPRT/mDsRed were generated. The expression of the fusion proteins was evaluated by flow cytometry, fluorescence microscopy, and Western blot analysis. The function of the fusion protein was confirmed in vitro by assessing 5-FC and 5-FU cytotoxicity. In vivo fluorine-19 magnetic resonance spectroscopy ((19)F MRS) was used to monitor the conversion of 5-FC to 5-FU in mice bearing the R3327-CD/mDsRed and R3327-CD/UPRT/mDsRed tumor xenografts.
resultsSensitivity to 5-FC and 5-FU was higher in cells stably expressing the CD/UPRT/mDsRed fusion gene than in cells stably expressing CD/mDsRed alone or wild-type cells. Whole tumor (19)F MRS measurements showed rapid conversion of 5-FC to 5-FU within 20 min after 5-FC was administered intravenously in both CD/mDsRed and CD/UPRT/mDsRed tumors with subsequent anabolism to cytotoxic fluoronucleotides (FNucs). CD/UPRT/mDsRed tumor was more efficient in these processes.
conclusionThis study demonstrates the utility of these tumor models stably expressing CD or CD/UPRT to non-invasively evaluate the efficacy of the transgene expression/activity by monitoring drug metabolism in vivo using MRS, with potential applications in preclinical and clinical settings.
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