Magnetic resonance imaging of perfusion in rat cerebral 9L tumor after nicotinamide administration

Abstract

Purpose: To investigate the effect of nicotinamide on normal brain and 9L tumor blood flow in the rat using magnetic resonance imaging (MRI) and arterial spin tagging. Methods and Materials: Using MRI at 7 Tesla, measurements of blood perfusion were determined from two-dimensional maps of intracerebral 9L rat tumors and normal Fischer rat brains. The spatial and temporal influence of nicotinamide, 500 mg/kg i.p., on cerebral blood flow (CBF) was studied in normal brain and tumors between 5 and 21 days after tumor implantation. The MRI CBF measurements employed a variable tip-angle–gradient-recalled echo (VTA-GRE-CBF) readout of the magnetization of the tissue slice. The VTA-GRE-CBF required 8 minutes for a blood flow image with inplane resolution of 250 μm × 500 μm × 2 mm. Results: Normal brain blood flow decreased following the administration of nicotinamide. In contrast, tumor blood flow remained unaffected in the time following nicotinamide administration. Consequently, the blood flowing in the tumor relative to that in normal brain demonstrated a significant and selective increase in response to nicotinamide administration. Relative tumor blood flow increased at 10 minutes after nicotinamide injection compared with predrug levels and remained elevated for at least 1 hour. Conclusion: The results suggest that nicotinamide will not enhance radiosensitivity of brain tumors. The results support the use of nicotinamide to improve delivery of anticancer therapeutics through its ability to selectively increase tumor blood flow relative to that in normal brain.