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

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.

• Authors: A Jacobs, J Voges, R Reszka, M Lercher, A Gossmann, L Kracht, C Kaestle, R Wagner, K Wienhard, W D Heiss
• Journal: Lancet (London, England) (Lancet) Vol. 358 Issue 9283 Pg. 727-9 (Sep 01 2001) ISSN: 0140-6736 [Print] England
• PMID: 11551583 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Letter, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Arabinofuranosyluracil
• fialuridine
• Thymidine Kinase

Topics

• Aged
• Antiviral Agents
• Arabinofuranosyluracil (analogs & derivatives)
• Gene Expression Regulation, Viral
• Genetic Therapy (methods)
• Glioblastoma (diagnostic imaging, 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)