HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, K.-H. Articles by Kim, B.-T. Search for Related Content PubMed PubMed Citation Articles by Lee, K.-H. Articles by Kim, B.-T.

Accuracy of Myocardial Sodium/Iodide Symporter Gene Expression Imaging with Radioiodide: Evaluation with a Dual-Gene Adenovirus Vector

¹ Department of Nuclear Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
² Program in Cardiovascular Gene Therapy, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

The sodium/iodide symporter (NIS) gene allows convenient reporter imaging with -cameras and free radioiodide. In this study, we investigated the accuracy of this technique for assessing myocardial gene expression in living rats by using a dual-gene adenovirus that expresses both NIS protein and enhanced green fluorescent protein (EGFP). Methods: Rats underwent myocardial injection with the dual-gene adenovirus (Ad.EGFP.NIS) or a control virus (Ad.EGFP). ¹²³I scintigraphy was performed at day 4, and ratios of cardiac counts to mediastinal count were measured. The site of radiouptake was localized by use of dual-isotope ²⁰¹Tl images, and radioiodide efflux rates were evaluated by dynamic imaging. The dependence of cardiac radiouptake on viral titers and the sensitivity of detection of cardiac radiouptake were investigated at various viral titers. The radioactivity, EGFP, and NIS protein expression sites were compared microscopically. The correlation of image-based uptake with fluorometric measurements of EGFP concentrations was assessed by regression analysis. Results: ¹²³I scintigraphy demonstrated clear focal myocardial uptake at the Ad.EGFP.NIS injection site, with relatively slow washout rates (3.3% ± 0.8%/h), despite the absence of organification. Image-based cardiac uptake increased in a viral titer–dependent manner, with a detection threshold of between 3 x 10⁶ and 1 x 10⁷ plaque-forming units. Western blotting showed titer-dependent increases in myocardial NIS protein expression. Tissue radioactivity levels approached 12.5-fold control levels and correlated closely with image-based uptake (r = 0.91; P < 0.0001). Histologic analysis confirmed the colocalization of radiouptake, EGFP fluorescence, and NIS staining. Image-based uptake showed a strong correlation with fluorometric measurements of myocardial EGFP concentrations (r = 0.81; P < 0.0001). Conclusion: Our results demonstrate that convenient myocardial gene imaging with -cameras and radioiodide is feasible with the NIS gene. Moreover, the use of this technique with a dual-gene vector appears to allow accurate assessment of the level of myocardial expression of a second gene of interest.

Key Words: reporter gene • gene therapy • myocardium • radioiodide • scintigraphy

Related articles in JNM:

THIS MONTH IN JNM

JNM 2005 46: 8a-9a. [Full Text]  

This article has been cited by other articles:

				K.-H. Jung, J.-Y. Paik, B.-H. Ko, and K.-H. Lee Mitogen-Activated Protein Kinase Signaling Enhances Sodium Iodide Symporter Function and Efficacy of Radioiodide Therapy in Nonthyroidal Cancer Cells J. Nucl. Med., December 1, 2008; 49(12): 1966 - 1972. [Abstract] [Full Text] [PDF]

				R. Vogels, D. Zuijdgeest, M. van Meerendonk, A. Companjen, G. Gillissen, J. Sijtsma, I. Melis, L. Holterman, K. Radosevic, J. Goudsmit, et al. High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector J. Gen. Virol., November 1, 2007; 88(11): 2915 - 2924. [Abstract] [Full Text] [PDF]

				K.-H. Lee, J.-S. Bae, S.-C. Lee, J.-Y. Paik, T. Matsui, K.-H. Jung, B.-H. Ko, and B.-T. Kim Evidence that Myocardial Na/I Symporter Gene Imaging Does Not Perturb Cardiac Function J. Nucl. Med., November 1, 2006; 47(11): 1851 - 1857. [Abstract] [Full Text] [PDF]

				M. R. Lewis A "New" Reporter in the Field of Imaging Reporter Genes: Correlating Gene Expression and Function of the Sodium/Iodide Symporter J. Nucl. Med., January 1, 2006; 47(1): 1 - 3. [Full Text] [PDF]

				D. D. Vadysirisack, D. H. Shen, and S. M. Jhiang Correlation of Na+/I- Symporter Expression and Activity: Implications of Na+/I- Symporter as an Imaging Reporter Gene J. Nucl. Med., January 1, 2006; 47(1): 182 - 190. [Abstract] [Full Text] [PDF]