title: 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.forename: A
authors.initials: A
authors.lastname: Jacobs
authors.forename: J
authors.initials: J
authors.lastname: Voges
authors.forename: R
authors.initials: R
authors.lastname: Reszka
authors.forename: M
authors.initials: M
authors.lastname: Lercher
authors.forename: A
authors.initials: A
authors.lastname: Gossmann
authors.forename: L
authors.initials: L
authors.lastname: Kracht
authors.forename: C
authors.initials: C
authors.lastname: Kaestle
authors.forename: R
authors.initials: R
authors.lastname: Wagner
authors.forename: K
authors.initials: K
authors.lastname: Wienhard
authors.forename: W D
authors.initials: WD
authors.lastname: Heiss
mesh_terms: D000368:Aged; D000998:Antiviral Agents; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging; D011237:Predictive Value of Tests; D013937:Thymidine Kinase / Q000235:genetics; D014055:Tomography, Emission-Computed; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase