This Article 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 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 Faivre, J. Articles by Bréchot, C. Search for Related Content PubMed PubMed Citation Articles by Faivre, J. Articles by Bréchot, C.

Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats

¹ Department of Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unit 370, Paris V University, CHU Necker, Paris; ² Department of Nuclear Medicine, Necker Hospital, Paris; ³ Institut National de la Santé et de la Recherche Médicale Unit 559, Faculty of Medicine La Timone, Marseille; ⁴ Laboratory HIFIH, UPRESS EA, University of Angers, Angers; and ⁵ Vectorologie et Transfert de Gènes, Centre National de la Recherche Scientifique UMR 8121, Institut Gustave-Roussy, Villejuif, France

Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.

This article has been cited by other articles:

				I. Peerlinck, A. Merron, P. Baril, S. Conchon, P. Martin-Duque, C. Hindorf, J. Burnet, M. Quintanilla, M. Hingorani, R. Iggo, et al. Targeted Radionuclide Therapy Using a Wnt-Targeted Replicating Adenovirus Encoding the Na/I Symporter Clin. Cancer Res., November 1, 2009; 15(21): 6595 - 6601. [Abstract] [Full Text] [PDF]

				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]

				G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]

				T Kogai, K Taki, and G A Brent Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826. [Abstract] [Full Text] [PDF]

				L. Chen, A. Altmann, W. Mier, H. Eskerski, K. Leotta, L. Guo, R. Zhu, and U. Haberkorn Radioiodine Therapy of Hepatoma Using Targeted Transfer of the Human Sodium/Iodide Symporter Gene J. Nucl. Med., May 1, 2006; 47(5): 854 - 862. [Abstract] [Full Text] [PDF]

				O. Dohan, A. De la Vieja, and N. Carrasco Hydrocortisone and Purinergic Signaling Stimulate Sodium/Iodide Symporter (NIS)-Mediated Iodide Transport in Breast Cancer Cells Mol. Endocrinol., May 1, 2006; 20(5): 1121 - 1137. [Abstract] [Full Text] [PDF]

				T. Petrich, L. Quintanilla-Martinez, Z. Korkmaz, E. Samson, H. J. Helmeke, G. J. Meyer, W. H. Knapp, and E. Potter Effective Cancer Therapy with the {alpha}-Particle Emitter [211At]Astatine in a Mouse Model of Genetically Modified Sodium/Iodide Symporter-Expressing Tumors Clin. Cancer Res., February 15, 2006; 12(4): 1342 - 1348. [Abstract] [Full Text] [PDF]