This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Dwyer, R. M. Articles by Morris, J. C. Search for Related Content PubMed PubMed Citation Articles by Dwyer, R. M. Articles by Morris, J. C.

In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter

Departments of ¹ Endocrinology and ² Nuclear Medicine, Mayo Clinic, Rochester, Minnesota and ³ Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona

Requests for reprints: John C. Morris, Department of Endocrinology and Internal Medicine, 200 First Street Southwest, Rochester, MN 55905.Phone: 507-284-2324; Fax: 507-266-4716; E-mail: morris.john{at}mayo.edu.

Purpose: Expression of the sodium iodide symporter (NIS) in the thyroid gland provides for effective imaging and treatment of thyroid cancer using radiolabeled iodide. Transfer of NIS into other tumors would expand the utility of this treatment to tumors of nonthyroid origin. MUC1 is a transmembrane glycoprotein that is overexpressed in many tumor types, including breast, pancreatic, and ovarian. The aim of this study was to create a construct containing NIS under the control of the MUC1 promoter to target expression specifically to MUC1-positive breast cancer cells.

Experimental Design: A replication-deficient adenoviral construct was created containing the MUC1 promoter followed by the human NIS gene. Iodide uptake assays, Western blot, and immunohistochemistry were used to confirm NIS expression and function. Breast cancer xenografts in mice were infected with Ad5/MUC1/NIS and then imaged and treated using radioiodide.

Results: A 58-fold increase in iodide uptake was observed in infected MUC1-positive T47D cells with no significant increase observed in MUC1-negative MDA-MB-231 cells or in cells infected with the control virus. The in vivo study yielded clear images of Ad/MUC1/NIS-infected tumor xenografts using ¹²³I. Administration of a therapeutic dose of ¹³¹I resulted in an 83% reduction in tumor volume, whereas control tumors continued to increase in size (P < 0.01).

Conclusions: These results show that the MUC1 promoter is capable of directing efficient and selective expression of the NIS gene in MUC1-positive breast tumor cells. This could potentially have applications for both imaging and therapy in a range of MUC1-positive tumor types.

Key Words: NIS • MUC1 • radioiodine • gene therapy • breast cancer

This article has been cited by other articles:

				A. Goel, S. K. Carlson, K. L. Classic, S. Greiner, S. Naik, A. T. Power, J. C. Bell, and S. J. Russell Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV({Delta}51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene Blood, October 1, 2007; 110(7): 2342 - 2350. [Abstract] [Full Text] [PDF]

				S. J. Lim, J. C. Paeng, S. J. Kim, S. Y. Kim, H. Lee, and D. H. Moon Enhanced Expression of Adenovirus-Mediated Sodium Iodide Symporter Gene in MCF-7 Breast Cancer Cells with Retinoic Acid Treatment J. Nucl. Med., March 1, 2007; 48(3): 398 - 404. [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]

				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]

				K. Hasegawa, L. Pham, M. K. O'Connor, M. J. Federspiel, S. J. Russell, and K.-W. Peng Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter. Clin. Cancer Res., March 15, 2006; 12(6): 1868 - 1875. [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]

				C. Garcia-Jimenez, M. A. Zaballos, and P. Santisteban DARPP-32 (Dopamine and 3',5'-Cyclic Adenosine Monophosphate-Regulated Neuronal Phosphoprotein) Is Essential for the Maintenance of Thyroid Differentiation Mol. Endocrinol., December 1, 2005; 19(12): 3060 - 3072. [Abstract] [Full Text] [PDF]