Virus-associated tumor imaging by induction of viral gene expression.

Abstract

PURPOSE:

EBV and other herpesviruses are associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced in vitro with several chemotherapeutic agents that promote viral lytic induction. The goal of this study is to image EBV-associated tumors by induction of viral TK expression with radiolabeled 2'-fluoro-2'-deoxy-beta-D-5-iodouracil-arabinofuranoside (FIAU).

EXPERIMENTAL DESIGN:

Immunoblot, luciferase reporter assay, and in vitro assay with [(14)C]FIAU were used to show the effects of bortezomib on the induction of lytic gene expression of EBV-associated tumor cells. In vivo imaging and ex vivo biodistribution studies with [(125)I]FIAU on EBV-associated tumors were done to visualize and confirm, respectively, the EBV(+) tumor-specific effects of bortezomib.

RESULTS:

In vitro assays with [(14)C]FIAU and ex vivo biodistribution studies with [(125)I]FIAU showed that uptake and retention of radiolabeled FIAU was specific for cells that express EBV-TK. Planar gamma imaging of EBV(+) Burkitt's lymphoma xenografts in severe combined immunodeficient mice showed [(125)I]FIAU localization within tumors following treatment with bortezomib.

CONCLUSIONS:

These results indicate the feasibility of imaging chemotherapy-mediated viral lytic induction by radiopharmaceutical-based techniques such as single photon emission computed tomography and positron emission tomography.

• Authors: De-Xue Fu, Yvette C Tanhehco, Jianmeng Chen, Catherine A Foss, James J Fox, Victor Lemas, Ja-Mun Chong, Richard F Ambinder, Martin G Pomper
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 5 Pg. 1453-8 (Mar 01 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17332288 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Boronic Acids
• Pyrazines
• Radiopharmaceuticals
• Arabinofuranosyluracil
• fialuridine
• Bortezomib
• Thymidine Kinase

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Arabinofuranosyluracil (analogs & derivatives)
• Boronic Acids (therapeutic use)
• Bortezomib
• Burkitt Lymphoma (diagnostic imaging, drug therapy, virology)
• Diagnostic Imaging
• Gene Expression
• Gene Transfer Techniques
• Genes, Viral
• Herpesvirus 4, Human (enzymology, genetics)
• Humans
• Immunoblotting
• Mice
• Neoplasms, Experimental (diagnostic imaging, drug therapy)
• Oncogenic Viruses (enzymology, genetics)
• Pyrazines (therapeutic use)
• Radionuclide Imaging
• Radiopharmaceuticals
• Reverse Transcriptase Polymerase Chain Reaction
• Thymidine Kinase (genetics, metabolism)