| 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
(Affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.)
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| 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 1 2007)
ISSN: 1078-0432 United States |
| PMID | 17332288
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
| Chemical References |
- Antineoplastic Agents
- Boronic Acids
- Pyrazines
- Radiopharmaceuticals
- bortezomib
- Arabinofuranosyluracil
- fialuridine
- Thymidine Kinase
|
| Topics |
- Animals
- Antineoplastic Agents
(therapeutic use)
- Arabinofuranosyluracil
(analogs & derivatives, diagnostic use)
- Boronic Acids
(therapeutic use)
- Burkitt Lymphoma
(drug therapy, radionuclide imaging, virology)
- Diagnostic Imaging
- Gene Expression
- Gene Transfer Techniques
- Genes, Viral
- Herpesvirus 4, Human
(enzymology, genetics)
- Humans
- Immunoblotting
- Mice
- Neoplasms, Experimental
(drug therapy, radionuclide imaging)
- Oncogenic Viruses
(enzymology, genetics)
- Pyrazines
(therapeutic use)
- Radiopharmaceuticals
(diagnostic use)
- Reverse Transcriptase Polymerase Chain Reaction
- Thymidine Kinase
(genetics, metabolism)
|
