A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions Journal Article


Authors: Xing, L.; Sun, X.; Deng, X.; Kotedia, K.; Zanzonico, P. B.; Ackerstaff, E.; Koutcher, J. A.; Ling, C. C.; Li, G. C.
Article Title: A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions
Abstract: Gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, has shown promise in clinical trials. In this preclinical study using stable cell lines and xenograft tumor models, we show that a triple-suicide-gene GDEPT approach produce enhanced therapeutic efficacy over previous methods. Importantly, all the three genes (thymidine kinase, cytosine deaminase and uracil phosphoribosyltransferase) function simultaneously as effectors for GDEPT and markers for multimodality molecular imaging (MMI), using positron emission tomography, magnetic resonance spectroscopy and optical (fluorescent and bioluminescent) techniques. It was demonstrated that MMI can evaluate the distribution and function/activity of the triple suicide gene. The concomitant expression of these genes significantly enhances prodrug cytotoxicity and radiosensitivity in vitro and in vivo. © 2013 Nature America, Inc. All rights reserved.
Keywords: controlled study; fluorouracil; nonhuman; positron emission tomography; animal cell; low drug dose; radiotherapy; animal experiment; animal model; gene function; in vivo study; in vitro study; molecular imaging; xenograft; rat; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; radiosensitivity; therapy effect; iodine 124; thymidine kinase; drug cytotoxicity; ganciclovir; fluorescence imaging; prostate carcinoma; cytosine deaminase; uracil phosphoribosyltransferase; flucytosine; optical imaging; gene directed enzyme prodrug therapy; gene-directed enzyme prodrug therapy
Journal Title: Cancer Gene Therapy
Volume: 20
Issue: 6
ISSN: 0929-1903
Publisher: Nature Publishing Group  
Date Published: 2013-06-01
Start Page: 358
End Page: 365
Language: English
DOI: 10.1038/cgt.2013.28
PROVIDER: scopus
PMCID: PMC3696018
PUBMED: 23722591
DOI/URL:
Notes: --- - "Export Date: 1 August 2013" - "CODEN: CGTHE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Gloria C Li
    122 Li
  2. Ligang Xing
    15 Xing
  3. Xuelong Deng
    14 Deng
  4. Pat B Zanzonico
    247 Zanzonico
  5. Jason A Koutcher
    236 Koutcher
  6. C Clifton Ling
    313 Ling
  7. Xiu Sun
    1 Sun