Application of 23Na MRI to monitor chemotherapeutic response in RIF-1 tumors

Effects of an alkylating anticancer drug, cyclophosphamide (Cp), on Na-23 signal intensity (Na-23 SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously - implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo Na-23 and H-1 magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both Na-23 SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between Na-23 SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in Na-23 SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased Na-23 and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and Na-23 SI were largely due to an increase in extracellular 23 space. Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses.