Volume 12, Issue 5, Pages 835-841 (November 2005) A Preclinical Large Animal Model of Adenovirus-Mediated Expression of the Sodium– Iodide Symporter for Radioiodide Imaging and Therapy of Locally Recurrent Prostate Cancer  Roisin M. Dwyer, Stephen M. Schatz, Elizabeth R. Bergert, Rae M. Myers, Mary E. Harvey, Kelly L. Classic, Michael C. Blanco, Craig S. Frisk, Ronald J. Marler, Brian J. Davis, Michael K. O'Connor, Stephen J. Russell, John C. Morris  Molecular Therapy  Volume 12, Issue 5, Pages 835-841 (November 2005) DOI: 10.1016/j.ymthe.2005.05.013 Copyright © 2005 The American Society of Gene Therapy Terms and Conditions

FIG. 1 Whole-body planar image of a dog (No. 385) that had received an intraprostatic injection of Ad5/CMV/NIS at (A) 5 h and (B) 24 h following 123I administration. (C) The control animal (No. 384) received intraprostatic injections of saline, followed 3 days later by iv administration of 3 mCi 123I. In each photo, a clear image was seen of the thyroid, salivary glands (where included), and stomach, which are known to express NIS. The urinary bladder is also apparent as a result of 123I excretion. In the animal that was injected with Ad5/CMV/NIS (A, B), there is also a clear image of the prostate. The prostate is not apparent in the control animal (C). Image (D) is a SPECT/CT fusion image showing 123I concentration in the prostate of a dog that had been injected with Ad5/CMV/NIS. Molecular Therapy 2005 12, 835-841DOI: (10.1016/j.ymthe.2005.05.013) Copyright © 2005 The American Society of Gene Therapy Terms and Conditions

FIG. 2 Immunohistochemical staining of tissue sections harvested at animal necropsy. (A) Prostate section from control animal (No. 384), with neutrophil and macrophage infiltration (original magnification 200×). (B) Prostate section from treated animal (No. 382), with lymphocytes and macrophages more predominant (original magnification 200×). (C) Fat necrosis and concomitant inflammatory response in prostate section from treated dog (original magnification 100×). (D) Bladder thrombi observed in treated dog (original magnification 100×). (E) Glycogen deposition in liver sections from treated dog (original magnification 100×) (was also observed in control animal). Molecular Therapy 2005 12, 835-841DOI: (10.1016/j.ymthe.2005.05.013) Copyright © 2005 The American Society of Gene Therapy Terms and Conditions

FIG. 3 Time course of experiment. Animals were given T3 tablets (0.7 μg/kg) for 8 days prior to undergoing a laparotomy and intraprostatic injection of virus. Blood samples were also collected prior to surgery. Three days later animals received an iv dose of 3 mCi 123I followed by serial imaging 1, 3, 5, 24, and 48 h later. One day following completion of imaging, animals were transferred to a dedicated facility for administration of a therapeutic dose of 131I followed by 7 days of observation. On day 13, blood samples were collected, necropsy was performed, and tissues were harvested for histopathological analysis. Molecular Therapy 2005 12, 835-841DOI: (10.1016/j.ymthe.2005.05.013) Copyright © 2005 The American Society of Gene Therapy Terms and Conditions