Virus-associated tumor imaging by induction of viral gene expression
DX Fu, YC Tanhehco, J Chen, CA Foss, JJ Fox… - Clinical cancer …, 2007 - AACR
DX Fu, YC Tanhehco, J Chen, CA Foss, JJ Fox, V Lemas, JM Chong, RF Ambinder…
Clinical cancer research, 2007•AACRPurpose: 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-β-d-5-iodouracil-arabinofuranoside (FIAU). Experimental Design: Immunoblot …
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-β-d-5-iodouracil-arabinofuranoside (FIAU). Experimental Design: Immunoblot …
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-β-d-5-iodouracil-arabinofuranoside (FIAU).
Experimental Design: Immunoblot, luciferase reporter assay, and in vitro assay with [14C]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 [125I]FIAU on EBV-associated tumors were done to visualize and confirm, respectively, the EBV(+) tumor–specific effects of bortezomib.
Results: In vitro assays with [14C]FIAU and ex vivo biodistribution studies with [125I]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 [125I]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.
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