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.
PURPOSE: We evaluated the feasibility of non-invasive imaging of recombinant adenovirus-mediated humansodium-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.
Authors: K J Fisher; K Jooss; J Alston; Y Yang; S E Haecker; K High; R Pathak; S E Raper; J M Wilson Journal: Nat Med Date: 1997-03 Impact factor: 53.440
Authors: A Ishii; Y Hagiwara; Y Saito; K Yamamoto; K Yuasa; Y Sato; K Arahata; S Shoji; I Nonaka; I Saito; Y Nabeshima; S Takeda Journal: Muscle Nerve Date: 1999-05 Impact factor: 3.217
Authors: S S Yaghoubi; L Wu; Q Liang; T Toyokuni; J R Barrio; M Namavari; N Satyamurthy; M E Phelps; H R Herschman; S S Gambhir Journal: Gene Ther Date: 2001-07 Impact factor: 5.250
Authors: A Boland; M Ricard; P Opolon; J M Bidart; P Yeh; S Filetti; M Schlumberger; M Perricaudet Journal: Cancer Res Date: 2000-07-01 Impact factor: 12.701
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