Cardiac reporter gene imaging using the human sodium/iodide symporter gene

Masao Miyagawa, Moritz Beyer, Bettina Wagner, Martina Anton, Christine Spitzweg, Bernd Gansbacher, Markus Schwaiger, Frank M. Bengel

Research output: Contribution to journalArticlepeer-review

Abstract

Imaging of reporter gene expression holds promise for noninvasive monitoring of cardiovascular molecular therapy. We investigated the feasibility of myocardial gene expression imaging in living rats using the human sodium/iodide symporter gene (hNIS) and widely available scintigraphic techniques. We injected adenovirus expressing hNIS under control of cytomegalovirus promoter (Ad hNIS) directly into left ventricular myocardium of Wistar rats. For detection of reporter gene expression, dynamic gamma-camera imaging was performed following intravenous injection of 123Iodide or 99mTechnetium. For both radiotracers, focal cardiac accumulation was identified as early as 10 min, and remained detectable until 2 hrs after injection, while it was not present in animals injected with LacZ control virus. Intensity of tracer accumulation gradually decreased when decreasing titers of Ad hNIS were applied. Treatment with sodium perchlorate (a blocker of hNIS) abolished cardiac tracer uptake after Ad hNIS-infection. Serial imaging after cardiac gene transfer demonstrated a peak of tracer signal between days 1 and 3, and a subsequent decrease until day 12. Postmortem analysis of hearts yielded significant correlation between in vivo radiotracer accumulation and ex vivo gamma-counting. Autoradiography demonstrated specific regional radioactivity in Ad hNIS-infected myocardial areas. hNIS offers a practical and reliable approach for myocardial gene expression imaging. Using suitable vectors, hNIS may be coexpressed with therapeutic genes or stably expressed in stem cells for future monitoring of cardiovascular molecular therapy.

Original languageEnglish (US)
Pages (from-to)195-202
Number of pages8
JournalCardiovascular research
Volume65
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Cardiac imaging
  • Gene expression
  • Gene therapy
  • Radionuclides
  • Reporter genes
  • Sodium/iodide transporter

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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