Effects of blood flow modifiers on tumor metabolism observedin vivoby proton magnetic resonance spectroscopic imaging

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Abstract
Perfusion plays a key role in tumor proliferation and therapeutic response. Tumor heterogeneity necessitates use of the highest spatial resolution to monitor metabolic correlates of blood flow changes. This is best achieved with1H NMR spectroscopy, which permits noninvasive acquisition of high resolution spectroscopic images (SI) of subcutaneous tumors in a relatively short scan time (e.g., 12‐25 μl voxels with signal‐to‐noise ratio 7:1 in 30 min at 4.7 T). This study seeks to identify1H spectroscopic indices of tumor blood flow. Proton SI of subcutaneous murine RIF‐1 tumors were recorded (a) before and after administration of nicotinamide (1 g/kg) toincreaseblood flow, and (b) before and after hydralazine (10 mg/kg) todecreaseflow. Nicotinamide produced a significant decrease in the total choline peak amplitudes, which subsequent high resolution NMR spectroscopy of tumor extracts revealed to be due to decreases in phosphocholine and glycerophosphocholine. The deamidation of nicotinamide to nicotinic acid, which is known to have hypolipidemic effects and to stimulate the formation of prostaglandins, may have sufficiently altered lipid metabolism to affect thein vivoconcentration of the NMR‐visible choline‐containing compounds. The main effect of hydralazine was a significant increase of lactate, which is consistent with a reduction of tumor blood flow.