Imaging transgene activity in vivo Journal Article


Authors: Gade, T. P. F.; Koutcher, J. A.; Spees, W. M.; Beattie, B. J.; Ponomarev, V.; Doubrovin, M.; Buchanan, I. M.; Beresten, T.; Zakian, K. L.; Le, H. C.; Tong, W. P.; Mayer-Kuckuk, P.; Blasberg, R. G.; Gelovani, J. G.
Article Title: Imaging transgene activity in vivo
Abstract: The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase-uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT+ cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings. ©2008 American Association for Cancer Research.
Keywords: controlled study; fluorouracil; nonhuman; nuclear magnetic resonance imaging; magnetic resonance imaging; accuracy; animal cell; mouse; animals; mice; animal tissue; gene expression; animal experiment; animal model; in vivo study; enzyme activity; cell line, tumor; hybrid protein; mice, nude; quantitative analysis; gene therapy; transgene; transplantation, heterologous; rats; transgenes; cytosine deaminase; uracil phosphoribosyltransferase; fluorine; carcinoma 256, walker
Journal Title: Cancer Research
Volume: 68
Issue: 8
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2008-04-15
Start Page: 2878
End Page: 2884
Language: English
DOI: 10.1158/0008-5472.can-07-6028
PUBMED: 18413756
PROVIDER: scopus
PMCID: PMC3043616
DOI/URL:
Notes: --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus"
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MSK Authors
  1. William M Spees
    5 Spees
  2. Juri Gelovani
    125 Gelovani
  3. William Ping-Yiu Tong
    158 Tong
  4. Ronald G Blasberg
    267 Blasberg
  5. Vladimir Ponomarev
    114 Ponomarev
  6. Hongbiao Carl Lekaye
    31 Lekaye
  7. Kristen L Zakian
    82 Zakian
  8. Jason A Koutcher
    268 Koutcher
  9. Bradley Beattie
    124 Beattie
  10. Terence P Gade
    13 Gade