Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus

Michael Mullerad, David P. Eisenberg, Timothy J. Akhurst, Prasad S. Adusumilli, Christopher C. Riedl, Amit Bhargava, Mithat Gonen, Ronald Finn, Peter T. Scardino, Yuman Fong

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalMolecular Imaging and Biology
Volume8
Issue number1
DOIs
StatePublished - Jan 2006

Bibliographical note

Funding 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.

Keywords

  • Fluorodeoxyglucose
  • Herpes virus
  • Hormonal therapy
  • Prediction

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