Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.
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.
Mullerad
Michael
M
Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Eisenberg
David P
DP
Akhurst
Timothy J
TJ
Adusumilli
Prasad S
PS
Riedl
Christopher C
CC
Bhargava
Amit
A
Gonen
Mithat
M
Finn
Ronald
R
Scardino
Peter T
PT
Fong
Yuman
Y
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
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18