Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas

Lancet. 2001 Sep 1;358(9283):727-9. doi: 10.1016/s0140-6736(01)05904-9.

Abstract

In clinical gene-therapy trials for recurrent glioblastomas, transduction of the herpes simplex virus type-1 thymidine kinase (HSV-1-tk) gene with subsequent prodrug activation by ganciclovir was found to be safe, but clinical response was poor. We used positron-emission tomography (PET) with I-124-labelled 2'-fluoro-2'-deoxy-1b-D-arabino-furanosyl-5-iodo-uracil ([124I]-FIAU)-a specific marker substrate for gene expression of HSV-1-tk-to identify the location, magnitude, and extent of vector-mediated HSV-1-tk gene expression in a phase I/II clinical trial of gene therapy for recurrent glioblastoma in five patients. The extent of HSV-1-tk gene expression seemed to predict the therapeutic response. The expression of an exogenous gene introduced by gene therapy into patients with gliomas can be monitored non-invasively by PET.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents*
  • Arabinofuranosyluracil / analogs & derivatives*
  • Gene Expression Regulation, Viral
  • Genetic Therapy / methods*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / therapy*
  • Herpesvirus 1, Human / genetics*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Predictive Value of Tests
  • Thymidine Kinase / genetics
  • Tomography, Emission-Computed
  • Transduction, Genetic / methods*

Substances

  • Antiviral Agents
  • Arabinofuranosyluracil
  • fialuridine
  • Thymidine Kinase