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.
Bibliographical noteFunding Information:
This study was supported in part by grant ROI CA 75416 from the National Institutes of Health, grant IMG0402501 from the Susan G. Komen Foundation, grant R25-CA96945 from the National Cancer Institute, and grant BC024118 from the US Army. The radiotracer was prepared in a facility constructed with support from Research Facilities Improvement Program Grant number C06 RR-11192.
- Herpes virus
- Hormonal therapy