Document Detail

Imaging a Genetically Engineered Oncolytic Vaccinia Virus (GLV-1h99) Using a Human Norepinephrine Transporter Reporter Gene.
MedLine Citation:
PMID:  19470726     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Oncolytic viral therapy continues to be investigated for the treatment of cancer, and future studies in patients would benefit greatly from a noninvasive modality for assessing virus dissemination, targeting, and persistence. The purpose of this study was to determine if a genetically modified vaccinia virus, GLV-1h99, containing a human norepinephrine transporter (hNET) reporter gene, could be sequentially monitored by [(123)I]metaiodobenzylguanidine (MIBG) gamma-camera and [(124)I]MIBG positron emission tomography (PET) imaging. EXPERIMENTAL DESIGN: GLV-1h99 was tested in human malignant mesothelioma and pancreatic cancer cell lines for cytotoxicity, expression of the hNET protein using immunoblot analysis, and [(123)I]MIBG uptake in cell culture assays. In vivo [(123)I]MIBG gamma-camera and serial [(124)I]MIBG PET imaging was done in MSTO-211H orthotopic pleural mesothelioma tumors. RESULTS: GLV-1h99 successfully infected and provided dose-dependent levels of transgene hNET expression in human malignant mesothelioma and pancreatic cancer cells. The time course of [(123)I]MIBG accumulation showed a peak of radiotracer uptake at 48 hours after virus infection in vitro. In vivo hNET expression in MSTO-211H pleural tumors could be imaged by [(123)I]MIBG scintigraphy and [(124)I]MIBG PET 48 and 72 hours after GLV-1h99 virus administration. Histologic analysis confirmed the presence of GLV-1h99 in tumors. CONCLUSION: GLV-1h99 shows high mesothelioma tumor cell infectivity and cytotoxic efficacy. The feasibility of imaging virus-targeted tumor using the hNET reporter system with [(123)I]MIBG gamma-camera and [(124)I]MIBG PET was shown in an orthotopic pleural mesothelioma tumor model. The inclusion of human reporter genes into recombinant oncolytic viruses enhances the potential for translation to clinical monitoring of oncolytic viral therapy.
Peter Brader; Kaitlyn J Kelly; Nanhai Chen; Yong A Yu; Qian Zhang; Pat Zanzonico; Eva M Burnazi; Rashid E Ghani; Inna Serganova; Hedvig Hricak; Aladar A Szalay; Yuman Fong; Ronald G Blasberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-05-26
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-02     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3791-801     Citation Subset:  IM    
Departments of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
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MeSH Terms
3-Iodobenzylguanidine / diagnostic use,  pharmacokinetics
Cell Line, Tumor
Cell Survival
Gamma Cameras
Genetic Engineering
Iodine Radioisotopes
Mesothelioma / metabolism,  pathology,  virology
Mice, Nude
Neoplasms, Experimental / metabolism*,  pathology,  radionuclide imaging
Norepinephrine Plasma Membrane Transport Proteins / genetics,  metabolism*
Oncolytic Viruses / genetics,  metabolism*,  physiology
Pancreatic Neoplasms / metabolism,  pathology,  virology
Positron-Emission Tomography
Transplantation, Heterologous
Vaccinia virus / genetics,  metabolism*,  physiology
Grant Support
Reg. No./Substance:
0/Iodine Radioisotopes; 0/Norepinephrine Plasma Membrane Transport Proteins; 77679-27-7/3-Iodobenzylguanidine

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