EBV Conference 2008 Guangzhou - Baylor College of Medicine

54 (RegID: 1139)
Dexue Fu
Institution: Department of Oncology, Johns Hopkins University School of Medicine
e-mail: dfu1@jhmi.edu
IMAGING EBV-ASSOCIATED NASOPHARYNGEAL CARCINOMA IN VIVO
:De-Xue Fu, Yvette Tanhehco, Jianmeng Chen, James Fox, Catherine Foss, Sridhar Nimmadda, George
Sgouros, Martin Pomper and Richard Ambinder
Oralabstract:
Epstein-Barr virus (EBV) has been identified in a wide variety of lymphomas and carcinomas. The
virus encodes kinases that phosphorylate nucleoside analogs such as
2'-deoxy-2'-fluoro-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU). We hypothesized that it might be
possible to use the viral enzyme to concentrate [125I]FIAU specifically within tumor cells harboring virus
and thus deliver imaging and therapeutic radiation. In previous study, we found that bortezomib
(Velcade) is a potent stimulator of viral kinase expression in EBV (+) lymphoma cell lines in vitro and
EBV-associated lymphoma can be imaged by induction of viral gene expression with bortezomib
treatment in vivo (Fu. D., et al. Clin Cancer Res 13, 1453-1458, 2007). Moreover a therapeutic effect
was demonstrated with [131I]FIAU in xenografts derived from EBV (+) human lymphoma and gastric
cancer cell lines as well as KSHV (+) primary effusion lymphoma (Fu. D., et al, Nature Medicine, 2008
Sep 7 [Epub ahead of print]). In this study, we extend those results to targeting of EBV-associated
nasopharyngeal carcinoma (NPC). Ex vivo bio-distribution studies with [125I]FIAU showed that uptake
and retention of [125I] FIAU is highly specific for NPC cells that are EBV positive upon lytic infection
but not when virus is in the latent state. Planar gamma imaging and SPECT/CT imaging with
[125I]FIAU of NPC-bearing SCID mice showed selective concentration of radiotracer in tumor tissue in
EBV-associated NPC when animals were pretreated with the bortezomib. We found dramatically
increased [125I] FIAU uptake within EBV (+) NPC at 72 hours after injection of [125I]FIAU. These
results indicate that treatment with bortezomib leads to selective concentration of radiolabeled FIAU in
the EBV-associated NPC xenografts and may provide a simple way for the localization, monitoring and
therapy of EBV-associated NPC that could be translated to the clinic.
EBV Conference 2008 Guangzhou
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