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

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 (123)Iodide or (99m)Technetium.

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.