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


CONCLUSIONS
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.
Yang
Hyun Suk
HS
Department of Internal Medicine (Cardiology), Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, 138-736 Seoul, South Korea.
Lee
Heuiran
H
Kim
Sung Jin
SJ
Lee
Won Woo
WW
Yang
You-Jung
YJ
Moon
Dae Hyuk
DH
Park
Seong-Wook
SW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009928:Organ Specificity; D010100:Oxygen / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D000099209:Sodium-Iodide Symporters
D010100:Oxygen; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D027981:Symporters; D013667:Technetium; D000099209:Sodium-Iodide Symporters