MONITORING THYMIDINE KINASE AND GANCICLOVIR-INDUCED CHANGES IN RAT MALIGNANT GLIOMA IN-VIVO BY NUCLEAR-MAGNETIC-RESONANCE IMAGING

We have used high resolution magnetic resonance imaging to monitor mal ignant rat BT4C gliomas in vivo following herpes simplex virus thymidi ne kinase gene and ganciclovir (GCV) treatment. Twenty-six female BDIX rats were used for the study including four controls. Serial magnetic resonance imaging was performed every 72 hours to quantify tumor volu me, transverse relaxation time (T-2), and apparent diffusion constant (ADC) of water in the tumors and in the contralateral brain. GCV treat ment was given twice a day, intraperitoneally, for 21 days. The glioma s exhibited low T-2 and ADC values (before treatment), compared to nor mal brain, indicating the presence of high cell density tumors. Follow ing GCV treatment, a regional increase in T-2 and ADC was observed as early as day 4 of the treatment, even though the tumor volume was stil l increasing. These observations suggested evolution of local necroses which were confirmed by histology. In a group of five tumor bearing r ats, retrovirus-producing packaging cell injections were given intratu morally to mimic clinically relevant gene therapy. In these cases, onl y small and short-lasting T-2 and ADC elevations were found following GCV treatment without an effect on the overall tumor growth and outcom e. Our results show that quantitative magnetic resonance imaging inclu ding T-2 and ADC, is superior to robust Volume measurements in predict ing an early response to retrovirus-mediated gene therapy in vivo.