A novel PET tracer for evaluation of gene therapy
- Cliniques Universitaires de Bruxelles-Hopital Erasme, Brussels (Belgium); and others
A promising approach of gene therapy for cancer consist in the transduction of neoplastic cells with the herpes virus thymidine-kinase gene (HSV-tk) which renders transduced cells sensitive to the lethal effect of anti-viral agent such as ganciclovir (GCV). Pet with adapted radiotracers represents an adequate tool to determine in vivo the level of HSV-tk expression and to establish the optimal protocol of gene and GCV administrations in human. We have developed a new potential PET tracer, 9-((1-[F-18]fluoro-3-hydroxy-2-propoxy)methyl)guanine [F-18]FHPG should theoretically accumulate in cells expressing HSV-tk. [F-18]FHPG was obtained by nucleophilic substitution on a ditosylate precursor followed by hydrolysis. To determine the biological behavior of this compound, we synthetized the corresponding non radioactive fluorinated analog (FHPG) and tested its inhibitory activity on HSV-tk transduced 9L gliosarcoma cells maintained in culture. FHPG at 100 {mu}M suppress cell growth by 50% while GCV and acyclovir induced 100% suppression at 10 and 100 {mu}M, respectively. We then tested the in vitro uptake of n.c.a. [F-18]FHPG in cultured cells transduced with HSV-tk or a control gene (neomycin). Ratio of [F-18]FHPG uptake in HSV-tk versus control cells was 240 after 6 hours of incubation. In vivo uptake of [F-18]FHPG was tested in experimental tumors obtained by stereotactical implantion of transduced 9L cells in the brain of male Fischer 344 rats. Ratio of [F-18]FHPG uptake in HSV-tk versus control tumors was 2.5, 3 hours after intravenous tracer injection. Uptake in HSV-tk tumor was 19-fold higher than in the cortex. We concluded that [F-18]FHPG is a promising PET tracer for the evaluation of gene therapy involving viral thymidine kinase genes.
- OSTI ID:
- 447746
- Report Number(s):
- CONF-960659-; ISSN 0161-5505; TRN: 97:000961-0026
- Journal Information:
- Journal of Nuclear Medicine, Vol. 37, Issue Suppl.5; Conference: 43. annual meeting of the Society of Nuclear Medicine, Denver, CO (United States), 3-6 Jun 1996; Other Information: PBD: May 1996
- Country of Publication:
- United States
- Language:
- English
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