Effects of nicotinamide and carbogen on tumour oxygenation, blood flow, energetics and blood glucose levels

Both host carbogen (95% oxygen/5% carbon dioxide) breathing and nicotinamid e administration enhance tumour radiotherapeutic response and are being re- evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) methods have been used to give i nformation on the effects of nicotinamide alone and in combination with hos t carbogen breathing on transplanted rat GH3 prolactinomas. Gradient recall ed echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (S E) MRI, sensitive to perfusion/flow, showed large signal intensity increase s with carbogen breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hyp oxia, induced a small increase in blood oxygenation but no detectable chang e in perfusion/flow. Carbogen combined with nicotinamide was no more effect ive than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (beta NTP/P-i) ratio, implying that the tumour cells normally receive sub-optimal substra te supply, and is consistent with either increased glycolysis and/or a swit ch to more oxidative metabolism. The most striking observation was the mark ed increase in blood glucose (twofold) induced by both nicotinamide and car bogen. Whether this may play a role in tumour radiosensitivity has yet to b e determined. (C) 2000 Cancer Research Campaign.