gms | German Medical Science

6-methylpurine is a purine analogon that constitutes the toxic metabolite in the gene therapy system using purine nucleoside phosphorylase as suicide enzyme (PNP and 6-MePdR). To assess the feasibility of this system for glioblastoma treatment we started a pilot trial with direct injection of 6-methylpurine into rat brain and into C6lacZ gliomas. In the C6lacZ glioma model tumor growth can vary widely between individual animals, even leading to spontaneous regression without therapy. We therefore introduced an extended craniectomy allowing for ultrasonographic monitoring of the tumors several times a week before and after the therapeutic intervention.

Female Wistar rats are narcotized and immobilized in a stereotactic frame. Under microscopical view cranial bone is removed to form a window of about 15x20 mm for ultrasonographic examination. After healing of the scalp C6lacZ cells are injected stereotactically. Tumor growth is monitored ulrasonographically for 10 to 14 days, then 6-methylpurine is injected into the tumor and the effects are followed by sonography for another 14 days. Finally histologic examination is performed. In the pilot therapy group, 6-methylpurine was injected directly into the rat brain and side effects were assessed histologically.

6-methylpurine leads to a necrotic area in cerebral tissue, its size correlates to the injected dose. Ultrasonographic assessment enables close monitoring of tumor growth kinetics with calculation of tumor volumes.

Sonographic examination of tumor volume is a useful and important adjunct for assessment of therapeutic effects in the C6lacZ rat glioma model. The pilot study revealed 6-methylpurine as a promising agent for local therapy. The ongoing study has to disclose the local treatment effects of 6-methylpurine on glioma tissue and whether sonography can help to distinguish between necrosis and growing tumor, compared to histology.