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Published on: March 13, 2018
Imaging a Genetically Engineered Oncolytic Vaccinia Virus (GLV-1h99) Using a Human Norepinephrine Transporter
Peter Brader1, Kaitlyn J Kelly, Nanhai Chen
1Departments of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
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.
Insights
This study shows that a modified vaccinia virus (GLV-1h99) can be tracked noninvasively using imaging techniques. This allows for monitoring of oncolytic viral therapy in cancer patients.
Area of Science:
- Oncology
- Virology
- Medical Imaging
Background:
- Oncolytic viral therapy is a promising cancer treatment.
- Noninvasive methods are needed to monitor virus activity in patients.
- GLV-1h99 is a modified vaccinia virus engineered with a reporter gene.
Purpose of the Study:
- To evaluate the feasibility of using [(123)I]MIBG gamma-camera and [(124)I]MIBG PET imaging to monitor a GLV-1h99 oncolytic virus.
- To assess virus dissemination, targeting, and persistence in cancer models.
Main Methods:
- GLV-1h99 was tested in mesothelioma and pancreatic cancer cell lines.
- Cytotoxicity and hNET reporter gene expression were analyzed.
- In vitro and in vivo imaging studies were performed using [(123)I]MIBG and [(124)I]MIBG in an orthotopic mesothelioma model.
Main Results:
- GLV-1h99 demonstrated dose-dependent hNET expression and cytotoxicity in cancer cells.
- Peak radiotracer uptake was observed 48 hours post-infection in vitro.
- In vivo imaging successfully visualized virus-targeted tumors 48-72 hours after GLV-1h99 administration.
Conclusions:
- GLV-1h99 exhibits high infectivity and efficacy against mesothelioma tumors.
- The hNET reporter system combined with [(123)I]MIBG and [(124)I]MIBG PET imaging is feasible for monitoring oncolytic viruses.
- Reporter genes enhance the clinical translation potential of oncolytic viral therapies.
