title: Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.
abstract: 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.
authors.affiliation: Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mullerad
authors.forename: David P
authors.initials: DP
authors.lastname: Eisenberg
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Akhurst
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Riedl
authors.forename: Amit
authors.initials: A
authors.lastname: Bhargava
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Ronald
authors.initials: R
authors.lastname: Finn
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014183:Transplantation, Heterologous
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18