In vivo radioiodide imaging and treatment of pancreatic cancer xenografts after MUC1 promoter-driven expression of the human sodium-iodide symporter.
OBJECTIVE
Mucin 1 (MUC1) is a transmembrane glycoprotein that is overexpressed in many tumor types, including breast, pancreatic, and ovarian cancer. The aim of this study was to create a construct containing sodium-iodide symporter (NIS) under the control of the 0.8-kb MUC1 promoter to infect pancreatic cancer cells both in vitro and in vivo, to investigate the potential for radioiodide imaging and ablation of this disease.


METHODS
We amplified the 797-bp MUC1 promoter by two-step nested PCR. Subsequently, a replication-deficient adenoviral construct was created containing the MUC1 promoter followed by the human NIS gene. Iodide uptake assays and immunofluorescence were used to confirm NIS expression and function. Pancreatic cancer xenografts in mice were infected with Ad/MUC1/NIS and then imaged and treated using radioiodide.


RESULTS
A 23- and 15.5-fold increase in iodide uptake was observed in Ad/MUC1/NIS-infected MUC1-positive Capan-2 and SW1990 cells with no significant increase observed in MUC1-negative Hela cells or in cells infected with the control virus. The in vivo study showed a clear image of Ad/MUC1/NIS-infected tumor xenografts using (125)I. Administration of a therapeutic dose of (131)I resulted in a regression in size to 76 +/- 15% of their original volume, whereas control tumors continued to increase in size to >200% of their original volume.


CONCLUSIONS
These results show that the 0.8-kb MUC1 promoter was successfully used to drive human NIS-targeted expression in pancreatic cancer cells, and Ad/MUC1/NIS-mediated radiotherapy can make pancreatic cancer xenografts in mice shrinking. This could potentially have applications for both imaging and therapy in other MUC1-positive tumors.
Chen
Ru F
RF
Department of Hepatobiliary Surgery, Second Affiliated Hospital, Sun Yat-sen University, GuangZhou, China.
Li
Zhi H
ZH
Pan
Qiu H
QH
Zhou
Jia J
JJ
Tang
Qi B
QB
Yu
Fen Y
FY
Zhou
Quan B
QB
Wang
Jie
J
Chen
Ji S
JS
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D027981:Symporters / Q000096:biosynthesis* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D007457:Iodine Radioisotopes; D018396:Mucin-1; D027981:Symporters; D000099209:Sodium-Iodide Symporters