Sodium iodide symporter (NIS)-mediated radiovirotherapy for pancreatic cancer.
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 (131)I radiotherapy in this tumor model.


METHODS
Subcutaneous human BxPC-3 pancreatic tumors were injected twice with MV-NIS. Viral infection, NIS expression, and intratumoral iodide uptake were quantitated with (123)I micro-SPECT/CT. Mice with MV-NIS-infected tumors were treated with 0, 37, or 74 MBq (131)I 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 (131)I.


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 (131)I 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 (131)I therapy. Stably transduced NIS-expressing BxPC-3 tumors exhibited rapid regression with > or = 18.5 MBq (131)I.


CONCLUSIONS
Delivery of (131)I 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 (131)I in this model was not due to a lack of radiosensitivity but rather to a nonuniform intratumoral distribution of MV-NIS infection.
Penheiter
Alan R
AR
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Wegman
Troy R
TR
Classic
Kelly L
KL
Dingli
David
D
Bender
Claire E
CE
Russell
Stephen J
SJ
Carlson
Stephanie K
SK
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008459:Measles virus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000628:therapy* / Q000821:virology; D027981:Symporters / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters