Uncoupling of fatty acid and glucose metabolism in malignant lymphoma: a PET study

Increased use of glucose through glycolysis is characteristic for neoplasti c growth while the significance of serum-free fatty acids for regulation of energy metabolism in cancer is poorly understood. We studied whether serum -free fatty acids (FFA) interfere with glycolytic metabolism of lymphoproli ferative neoplasms as assessed with 2-F-18-fluoro-2-deoxy-D-glucose ([F-18] FDG) and positron emission tomography (PET). Twelve patients with newly dia gnosed non-Hodgkin's lymphoma (n = 9) or Hodgkin's disease (n = 3) particip ated in this study before start of oncologic treatment. Each patient underw ent two [F-18]FDG PET studies within 1 week after overnight fast: once duri ng high fasting serum FFA concentrations and once after reduction of serum FFA by administration of acipimox. Acipimox is a nicotinic acid derivative that inhibits lipolysis in peripheral tissues and induces a striking reduct ion in circulating FFA concentration. In all cases, dynamic PET imaging ove r the tumour area was performed for 60 min after injection of [F-18]FDG. Bo th graphical analysis (rMR(FDG)) and single scan approach (SUV) were used t o compare tumour uptake of [F18]FDG under high fasting FFA concentrations a nd after pharmacologically decreased FFA concentrations. Serum FFA concentr ations were reduced significantly from 0.92 +/- 0.42 mmol l(-1) at baseline to 0.26 +/- 0.31 mmol l(-1) after acipimox administration (P = 0.0003). Pl asma glucose, serum insulin and lactate concentrations were similar during both approaches. The retention of glucose analogue [F-18]FDG in tumour was similar between baseline and acipimox studies. Median rMR(FDG) of a total o f 12 involved lymph nodes in 12 patients was 21.9 mu mol 100 g(-1) min(-1) (range 8.7-82.5) at baseline and 20.1 mu mol 100 g(-1) min(-1) (range 10.7- 81.7) after acipimox, The respective values for median SUV were 7.8 (range 3.6-18.6) and 6.0 (range 4.1-20.2). As expected, [F-18]FDG uptake in myocar dium was clearly enhanced by acipimox due to reduction of circulating FFAs. In conclusion, blood fatty acids appear to have minor significance for [F- 18]FDG uptake in lymphoma. This suggests that glucose utilization is uncoup led of FFA metabolism and indicates that glucose-free fatty acid cycle does not operate in lymphomatous tissue. Glucose appears to be the preferred su bstrate for energy metabolism in tumours, in spite of the high supply of FF As in the fasting state. Although acipimox and other anti-lipolytic drugs h ave potential for treatment of catabolic state induced by cancer, they are not likely to interfere with tumour energy metabolism which is fuelled by g lucose.