Sodium iodide symporter (NIS)-mediated radiovirotherapy for pancreatic cancer.
AJR Am J Roentgenol
; 195(2): 341-9, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20651188
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 (131)I radiotherapy in this tumor model. MATERIALS ANDMETHODS:
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.CONCLUSION:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Simportadores
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Radioisótopos do Iodo
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Vírus do Sarampo
Tipo de estudo:
Guideline
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
AJR Am J Roentgenol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos