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PLoS One ; 7(3): e32871, 2012.
Article in English | MEDLINE | ID: mdl-22412937

ABSTRACT

Oncolytic adenoviruses can be engineered for better tumor selectivity, gene delivery and be armed for imaging and concentrating radionuclides into tumors for synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of transgene expression and for treatment of infected tumors by radioiodine. Ad5/3-hTERT-hNIS efficiently killed prostate cancer cells and induced iodine uptake in vitro and in vivo after intratumoral virus administration. Survival of mice treated with intravenous Ad5/3-hTERT-hNIS significantly prolonged survival over mock or radioiodine only but the combination of virus with radioiodine was not more effective than virus alone. Temporal and spatial changes in hNIS-expression during therapy were detected with SPECT, demonstrating feasibility of evaluation of the combination therapy with hNIS-expressing adenoviruses and radioiodide.


Subject(s)
Adenoviridae/genetics , Genetic Vectors/genetics , Iodine Radioisotopes/metabolism , Multimodal Imaging , Oncolytic Viruses/genetics , Positron-Emission Tomography , Symporters/genetics , Tomography, X-Ray Computed , Animals , Cell Line , Gene Expression , Genetic Therapy , Genetic Vectors/administration & dosage , Humans , Injections, Intravenous , Iodine Radioisotopes/therapeutic use , Male , Mice , Mice, Nude , Molecular Imaging , Oncolytic Virotherapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/mortality , Prostatic Neoplasms/therapy , Symporters/metabolism , Treatment Outcome
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