Sodium iodide symporter (NIS)-mediated radiovirotherapy for pancreatic cancer

Alan R. Penheiter, Troy R. Wegman, Kelly L. Classic, David Dingli, Claire E. Bender, Stephen J. Russell, Stephanie K. Carlson

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

OBJECTIVE. We have previously shown the therapeutic efficacy of an engineered oncolytic measles virus expressing the sodium iodide symporter reporter gene (MV-NIS) in mice with human pancreatic cancer xenografts. The goal of this study was to determine the synergy between MV-NIS-induced oncolysis and NIS-mediated 131I radiotherapy in this tumor model. MATERIALS AND METHODS. Subcutaneous human BxPC-3 pancreatic tumors were injected twice with MV-NIS. Viral infection, NIS expression, and intratumoral iodide uptake were quantitated with 123I micro-SPECT/CT. Mice with MV-NIS-infected tumors were treated with 0, 37, or 74 MBq 131I and monitored for tumor progression and survival. Additional studies were performed with stable NIS-expressing tumors (BxPC-3-NIS) treated with 0, 3.7, 18.5, 37, or 74 MBq of 131I. RESULTS. Mice treated with intratumoral MV-NIS exhibited significant tumor growth delay (p < 0.01) and prolonged survival (p = 0.02) compared with untreated mice. Synergy between MV-NIS-induced oncolysis and NIS-mediated 131I ablation was not seen; however, a significant correlation was observed between NIS-mediated intratumoral iodide localization (% ID/g) and peak tumor volume reduction (p = 0.04) with combination MV-NIS and 131I therapy. Stably transduced NIS-expressing BxPC-3 tumors exhibited rapid regression with ≥ 18.5 MBq 131I. CONCLUSION. Delivery of 131I radiotherapy to NIS-expressing tumors can be optimized using micro-SPECT/CT imaging guidance. Significant hurdles exist for NIS as a therapeutic gene for combined radiovirotherapy in this human pancreatic cancer model. The lack of synergy observed with MV-NIS and 131I in this model was not due to a lack of radiosensitivity but rather to a nonuniform intratumoral distribution of MV-NIS infection.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalAmerican Journal of Roentgenology
Volume195
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • I
  • Measles virus
  • Pancreatic cancer
  • Sodium iodide symporter (NIS)
  • hNIS

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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