Imaging of human sodium-iodide symporter gene expression mediated by recombinant adenovirus in skeletal muscle of living rats

Abstract

Purpose: We evaluated the feasibility of non-invasive imaging of recombinant adenovirus-mediated human sodium-iodide symporter (hNIS) gene expression by (99m)TcO(4)(-) scintigraphy in skeletal muscle of rats.

Methods: Replication-defective recombinant adenovirus encoding hNIS gene [Rad-CMV-hNIS 5x10(7), 2x10(8) or 1x10(9) plaque forming units (pfu)] or beta-galactosidase gene (Rad-CMV-LacZ 1x10(9) pfu) was injected into the right biceps femoris muscle of rats ( n=5-6 for each group). Three days after gene transfer, scintigraphy was performed using a gamma camera 30 min after injection of (99m)TcO(4)(-) (1.85 MBq). An additional two rats injected with 1x10(9) pfu of Rad-CMV-hNIS underwent (99m)TcO(4)(-) scintigraphy with sodium perchlorate. After the imaging studies, rats were sacrificed for assessment of the biodistribution of (99m)TcO(4)(-) and measurement of hNIS mRNA expression.

Results: In all the rats injected with 1x10(9) pfu of Rad-CMV-hNIS, hNIS expression was successfully imaged by (99m)TcO(4)(-) scintigraphy, while rats injected with Rad-CMV-LacZ or lower doses of Rad-CMV-hNIS failed to show uptake. The biodistribution studies indicated that a significantly different amount of (99m)TcO(4)(-) was retained in the liver ( p<0.001) and the right muscle ( p<0.05), with the highest uptake in rats injected with 1x10(9) pfu of Rad-CMV-hNIS. The muscular hNIS mRNA level quantified by real-time reverse transcription-polymerase chain reaction was significantly higher in rats injected with 1x10(9) pfu of Rad-CMV-hNIS ( p<0.05), with a positive correlation with the imaging counts ( r=0.810, p<0.05) and the biodistribution ( r=0.847, p<0.001). Hot spots in rats injected with 1x10(9) pfu of Rad-CMV-hNIS were specifically inhibited by sodium perchlorate.

Conclusion: This study illustrated that (99m)TcO(4)(-) scintigraphy can monitor Rad-CMV-hNIS-mediated gene expression in skeletal muscle of rats, non-invasively and quantitatively.