Journal
AMERICAN JOURNAL OF ROENTGENOLOGY
Volume 195, Issue 2, Pages 341-349Publisher
AMER ROENTGEN RAY SOC
DOI: 10.2214/AJR.09.3672
Keywords
I-131; hNIS; measles virus; pancreatic cancer; sodium iodide symporter (NIS)
Funding
- National Cancer Institute [K08 CA103859-03A1, P50 CA102701]
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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 I-131 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 I-123 micro-SPECT/CT. Mice with MV-NIS-infected tumors were treated with 0, 37, or 74 MBq I-131 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 I-131. 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 I-131 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 I-131 therapy. Stably transduced NIS-expressing BxPC-3 tumors exhibited rapid regression with = 18.5 MBq I-131. CONCLUSION. Delivery of I-131 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 I-131 in this model was not due to a lack of radiosensitivity but rather to a nonuniform intratumoral distribution of MV-NIS infection.
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