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2006:
Mullerad Michael; Eisenberg David P; Akhurst Timothy J; Adusumilli Prasad S; Riedl Christopher C; Bhargava Amit; Gonen Mithat; Finn Ronald; Scardino Peter T; Fong Yuman
Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging 2006;
8(
1):.
Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.
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