In vivo radioiodide imaging and treatment of breast cancer xenografts after MUC1-driven expression of the sodium iodide symporter.
OBJECTIVE
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.


METHODS
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 (123)I. Administration of a therapeutic dose of (131)I 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.
Dwyer
Roisin M
RM
Department of Endocrinology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
Bergert
Elizabeth R
ER
O'connor
Michael K
MK
Gendler
Sandra J
SJ
Morris
John C
JC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D018396:Mucin-1; D027981:Symporters; D000099209:Sodium-Iodide Symporters