ECE2009 Poster Presentations Endocrine tumours and neoplasia (53 abstracts)
Image-guided radioiodine therapy of HCC following AFP-promoter targeted in vivo sodium iodide symporter (NIS) gene transfer
Katrin Klutz 1 , Michael J Willhauck 1 , Nathalie Wunderlich 1 , Christian Zach 1 , Reingard Senekowitsch-Schmidtke 2 , Martina Anton 2 , Burkhard Göke 1 & Christine Spitzweg 1
1Ludwig-Maximilians-University, Munich, Germany; 2Technische Universität, Munich, Germany.
Due to limited treatment options the prognosis of patients with advanced hepatocellular cancer (HCC) has remained poor. We therefore examined the feasibility of radioiodine therapy of HCC after human sodium iodide symporter (hNIS) gene transfer, using the tumor-specific alpha-fetoprotein (AFP) promoter for transcriptional targeting. For this purpose NIS gene transfer was performed in vivo in human HCC cell (HepG2) xenografts, using replication-deficient adenoviral vectors carrying the NIS gene linked to the AFP-promoter fragment (Ad5-AFP-NIS). Functional NIS expression was confirmed by immunostaining as well as in vivo 123I gamma-camera imaging followed by application of a therapeutic 131I dose. HepG2 cell xenografts in nude mice injected intratumorally with Ad5-AFP-NIS accumulated 10–15% ID/g (percentage injected dose per gram tumor tissue; 3×109 PFU) with an average biological half-life of 8.3±1.8 h resulting in a tumor-absorbed dose of 215±77 mGy/MBq. After Ad5-AFP-NIS-mediated NIS gene transfer in HepG2 cell xenografts administration of a therapeutic dose of 55.5 MBq of 131I resulted in a significant reduction of tumor growth associated with significantly improved survival. We conclude that a therapeutic effect of 131I was demonstrated in vivo in HCC cell xenografts after adenovirus-mediated induction of tumor-specific iodide accumulation by AFP promoter-directed hNIS expression.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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