Virus-associated tumor imaging by induction of viral gene expression

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1453-1458
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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