Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas.
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.
Jacobs
A
A
Voges
J
J
Reszka
R
R
Lercher
M
M
Gossmann
A
A
Kracht
L
L
Kaestle
C
C
Wagner
R
R
Wienhard
K
K
Heiss
W D
WD
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*
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase