Image-guided radioiodide therapy of medullary thyroid cancer after carcinoembryonic antigen promoter-targeted sodium iodide symporter gene expression

Christine Spitzweg, Claire H. Baker, Elizabeth R. Bergert, M. K. O'Connor, John C. Morris

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

In contrast to follicular cell-derived thyroid cancer, medullary thyroid cancer (MTC) remains difficult to treat because of its unresponsiveness to radioiodine therapy, or to conventional chemo- and radiotherapy. We therefore examined the feasibility of radioiodine therapy of MTC after human sodium iodide symporter (hNIS) gene transfer, using the tumor-specific carcinoembryonic antigen (CEA) promoter for transcriptional targeting. NIS gene transfer was performed in vivo in human MTC cell (TT) xenografts, using adenoviral vectors carrying the NIS gene linked to the cytomegalovirus promoter (Ad5-CMV-NIS) or a CEA promoter fragment (Ad5-CEA-NIS). Functional NIS expression was confirmed by immunostaining as well as in vivo 123I γ-camera imaging followed by application of a therapeutic 131I dose. TT cell xenografts in nude mice injected intratumorally with Ad5-CEA-NIS accumulated 7.5 ± 1.2% ID/g (percentage injected dose per gram tumor tissue; 5 × 108 PFU) and 12 ± 2.95% ID/g (1 × 109 PFU) with an average biological half-life of 6.1 ± 0.8 and 23.6 ± 3.7 hr, respectively, as compared with accumulation of 8.4 ± 0.9% ID/g with a biological half-life of 12 ± 8 hr after application of Ad5-CMV-NIS (5 × 108 PFU). After Ad5-CEA-NIS-mediated NIS gene transfer in TT cell xenografts administration of a therapeutic dose of 111 MBq (3 mCi) of 131I resulted in a significant reduction of tumor growth associated with significantly lower calcitonin serum levels in treated mice as well as improved survival. We conclude that a therapeutic effect of 131I was demonstrated in vivo in MTC cell xenografts after adenovirus-mediated induction of tumor-specific iodide accumulation by CEA promoter-directed hNIS expression.

Original languageEnglish (US)
Pages (from-to)916-924
Number of pages9
JournalHuman gene therapy
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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