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

Michael Mullerad1, David P Eisenberg, Timothy J Akhurst

  • 1Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Insights

Androgen enhances herpes simplex virus (HSV) oncolytic therapy for prostate cancer. Positron emission tomography (PET) imaging of FDG uptake predicts treatment response, aiding patient selection for this innovative cancer therapy.

Area of Science:

  • Oncology
  • Virology
  • Molecular Imaging

Background:

  • Oncolytic herpes simplex virus (HSV) gene therapy shows promise for cancer treatment.
  • Androgen signaling influences prostate cancer progression and therapy response.
  • Positron emission tomography (PET) with 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) detects metabolic changes in tumors.

Purpose of the Study:

  • To investigate if androgen-induced cellular changes enhance oncolytic HSV therapy efficacy in prostate cancer.
  • To determine if FDG-PET imaging can predict tumor response to oncolytic HSV therapy.

Main Methods:

  • Utilized an androgen-dependent prostate cancer cell line and in vivo models.
  • Administered HSV oncolytic therapy with and without androgen manipulation (orchiectomy).
  • Assessed viral replication, cell kill, and tumor response using FDG-PET imaging.

Main Results:

  • Androgen treatment significantly increased in vitro cell kill (74%) and in vivo viral yield (2.4-fold) following HSV therapy.
  • FDG-PET imaging demonstrated high FDG accumulation in responsive tumors and low uptake after orchiectomy, correlating with treatment efficacy (p = 0.002).

Conclusions:

  • Androgen enhances the efficacy of oncolytic HSV therapy in prostate cancer.
  • FDG-PET is a viable noninvasive imaging method to predict tumor response to oncolytic HSV therapy.
  • This approach can guide patient selection for targeted oncolytic viral therapy in prostate cancer.

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