ASSESSMENT OF GANCICLOVIR TOXICITY TO EXPERIMENTAL INTRACRANIAL GLIOMAS FOLLOWING RECOMBINANT ADENOVIRAL-MEDIATED TRANSFER OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE BY MAGNETIC-RESONANCE-IMAGING AND PROTON MAGNETIC-RESONANCE SPECTROSCOPY

Magnetic resonance imaging and in vivo localized H-1 magnetic resonanc e spectroscopy were used to evaluate a gene therapy approach for treat ing experimental brain tumors. This approach involved the use of an ad enoviral vector to transfer the herpes simplex virus thymidine kinase (HSVtk) gene into intracerebral 9L gliosarcomas in rats followed by sy stemic administration of the antiherpetic agent ganciclovir. Magnetic resonance imaging quantitation of changes in intracranial 9L tumor dou bling times revealed a significant variation in therapeutic response. Localized H-1 magnetic resonance spectra of 9L tumors treated with Ad. RSVtk/ganciclovir revealed a dramatic increase in the resonance intens ity at 0.9-1.3 ppm, corresponding to mobile lipids and/or lactate. Cha nges in intracranial tumor doubling times correlated with changes in H -1 tumor magnetic resonance spectra, suggesting that specific changes in tumor metabolite levels may be predictive of the effectiveness of t his gene therapy approach.