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Multimodality Noninvasive Imaging of Gene Transfer Using the Human Sodium Iodide Symporter

¹ Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
² Department of Otolaryngology-Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
³ Division of Nuclear Medicine, Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa

View larger version (24K): [in a new window]   FIGURE 1. Imaging of hNIS gene transfer using 125I- and autoradiography. (A) Upper panel demonstrates the high correlation between average pixel intensity per well and Ad-hNIS viral titer. Bold line denotes linear regression from 0 to 20 MOI. Lower panel shows increasing signal of autoradiographs with increasing Ad-hNIS titer. (B) Upper panel demonstrates the high correlation that exists between average pixel intensity per well and activity of added 125I-. Line denotes linear regression of pixel intensity per well vs. 125I- activity. Lower panel shows increasing signal intensity with increasing 125I- activity in MB-435 cells infected with 25 MOI of Ad-hNIS. Data are expressed as the mean ± SD of 3 replicates and are representative of at least 3 separate experiments.

View larger version (27K): [in a new window]   FIGURE 2. Imaging of hNIS gene transfer using 99mTcO4- and -camera scintigraphy. (A) Upper panel demonstrates the positive correlation between cpm per well and Ad-hNIS viral titer. Lower panel shows -camera images with increasing signal as adenovirus titer is increased. (B) Upper panel demonstrates the high correlation between cpm per well and activity of added 99mTcO4-. Line shows linear regression of cpm per well vs. 99mTcO4- activity. Lower panel shows -camera images of Ad-hNIS-infected MB-435 cells. Signal increased with increasing activities of 99mTcO4- at a fixed viral titer. Data are expressed as the mean ± SD of 3 replicates and are representative of at least 3 separate experiments.

View larger version (23K): [in a new window]   FIGURE 3. Imaging of hNIS gene transfer using 76Br- and PET. (A) Upper panel demonstrates the high correlation between total counts per well and Ad-hNIS titer. Line denotes linear regression. Lower panel shows PET images and increasing signal as adenovirus titer is increased. (B) Upper panel demonstrates high correlation between total counts per well and activity of added 76Br-. Line denotes linear regression. Lower panel shows PET images. Signal increases as 76Br- activity is increased at a fixed viral titer. Data are representative of 2 separate experiments.

View larger version (15K): [in a new window]   FIGURE 4. Relationship between NIS-mediated 125I- accumulation (expressed as average pixel intensity per well as determined by autoradiography) and eGFP signal in MB-435 cells infected with dual-expressing Ad-hNIS-eGFP adenovirus. A linear correlation exists up to approximately 20 MOI.