Non-invasive bioluminescence imaging of myoblast-mediated hypoxia-inducible factor-1 alpha gene transfer

Olivier Gheysens, Ian Y. Chen, Martin Rodriguez-Porcel, Carmel Chan, Julia Rasooly, Caroline Vaerenberg, Ramasamy Paulmurugan, Juergen K. Willmann, Christophe Deroose, Joseph Wu, Sanjiv S. Gambhir

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: We tested a novel imaging strategy, in which both the survival of transplanted myoblasts and their therapeutic transgene expression, a recombinant hypoxia-inducible factor- 1α (HIF-1α-VP2), can be monitored using firefly luciferase (fluc) and Renilla luciferase (hrl) bioluminescence reporter genes, respectively. Procedures: The plasmid pUbi-hrl-pUbi-HIF-1α-VP2, which expresses both hrl and HIF-1α-VP2 using two ubiquitin promoters, was characterized in vitro. C2c12 myoblasts stably expressing fluc and transiently transfected with pUbi-hrl-pUbi-HIF-1α-VP2 were injected into the mouse hindlimb. Both hrl and fluc expression were monitored using bioluminescence imaging (BLI). Results: Strong correlations existed between the expression of hRL and each of HIF-1α-VP2, VEGF, and PlGF (r 2>0.83, r 2>0.82, and r 2>0.97, respectively). In vivo, both transplanted cells and HIF-1α-VP2 transgene expression were successfully imaged using BLI. Conclusions: An objective evaluation of myoblast-mediated gene transfer in living mice can be performed by monitoring both the survival and the transgene expression of transplanted myoblasts using the techniques developed herein.

Original languageEnglish (US)
Pages (from-to)1124-1132
Number of pages9
JournalMolecular Imaging and Biology
Volume13
Issue number6
DOIs
StatePublished - Dec 1 2011

Keywords

  • Bioluminescence imaging
  • Cell-mediated gene transfer
  • Hypoxia-inducible factor-1α
  • Molecular imaging

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Gheysens, O., Chen, I. Y., Rodriguez-Porcel, M., Chan, C., Rasooly, J., Vaerenberg, C., Paulmurugan, R., Willmann, J. K., Deroose, C., Wu, J., & Gambhir, S. S. (2011). Non-invasive bioluminescence imaging of myoblast-mediated hypoxia-inducible factor-1 alpha gene transfer. Molecular Imaging and Biology, 13(6), 1124-1132. https://doi.org/10.1007/s11307-011-0471-9