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Mapping the in vivo distribution of herpes simplex virions
D Schellingerhout1, A Bogdanov, E Marecos
1Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Charlestown 02129, USA.
Abstract:
We describe a method for labeling enveloped viral particles with a radiotracer, indium-111, allowing labeled viruses to be traced in vivo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 microCi/10(9) PFU. The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated (111)In had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 2.87 +/- 0.54% ID/g; liver, 2.60 +/- 0.51% ID/g; kidney, 0.98 +/- 0.31% ID/g; lung, 0.57 +/- 0.10% ID/g; [corrected] and lower amounts in other organs. Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging.
Insights
Researchers developed a method to label enveloped viruses, like herpes simplex virus (HSV), with indium-111 for in vivo tracking using nuclear imaging. This technique accurately assesses viral biodistribution without compromising infectivity.
Area of Science:
- Nuclear Medicine
- Virology
- Biomedical Imaging
Background:
- Assessing viral particle biodistribution in vivo is crucial for understanding infection dynamics and developing targeted therapies.
- Current methods for tracking viral spread often lack the resolution or sensitivity for quantitative analysis.
Purpose of the Study:
- To develop and validate a method for radiolabeling enveloped viruses using indium-111 for in vivo nuclear imaging.
- To evaluate the efficiency, infectivity, and biodistribution of radiolabeled herpes simplex virus (HSV).
Main Methods:
- Herpes simplex virus (HSV) particles were labeled with the radiotracer indium-111.
- Labeling efficiency and specific activity were determined.
- Infectivity assays were performed on labeled HSV.
- In vivo nuclear imaging was used to track the biodistribution of radiolabeled HSV in animals post-intravenous administration.
Main Results:
- A labeling efficiency of 83% was achieved for HSV, with a specific activity of 30 microCi/10(9) PFU.
- The radiolabeling procedure did not significantly reduce viral infectivity.
- In vivo imaging demonstrated rapid accumulation in the liver and redistribution to the spleen within 12-24 hours.
- Quantitative analysis showed specific organ distribution percentages, with spleen and liver being primary accumulation sites.
Conclusions:
- The described method enables effective radiolabeling of enveloped viruses with indium-111.
- This technique allows for qualitative and quantitative assessment of viral biodistribution using nuclear imaging.
- The method preserves viral infectivity and provides valuable insights into in vivo viral dynamics.