Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: The cellular basis for cardiac gene imaging

Frank M. Bengel, Martina Anton, Norbert Avril, Thomas Brill, Ngoc Nguyen, Roland Haubner, Elisabeth Gleiter, Bernd Gansbacher, Markus Schwaiger

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue. Methods and Results - The combination of the herpesvirus thymidine kinase reporter gene (HSVI-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [14C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained 125I]FIAU was injected intravenously 3 days later, and animals were killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3.4±2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (

Original languageEnglish (US)
Pages (from-to)948-950
Number of pages3
JournalCirculation
Volume102
Issue number9
StatePublished - Aug 29 2000
Externally publishedYes

Keywords

  • Arabinofuranosyluracil
  • Gene therapy
  • Genes, reporter
  • Imaging
  • Radioisotopes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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