Abstract
Twenty-six patients with gliomas of WHO-grades two to four were examined with dynamic positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG rate constants and derived glucose metabolic rates (MRdyn) were determined in solid tumor tissue and in tumor-free brain tissue. In addition, glucose metabolism was also calculated from single scans recorded 30 to 40 min after injection (MRstat).
All three rate constants, K1, k2, and k3, were significantly correlated with MRdyn in tumor-free brain. In contrast, in gliomas only k3 was significantly correlated with MRdyn. The ratio of k3 in tumors to k3 in tumor-free brain was also significantly related to histological tumor grade. The results indicate that FDG uptake in brain tumors is governed by FDG phosphorylation and is rather independent from the variation of FDG transport. A comparison between glucose metabolic rates calculated by an autoradiographic approach (MRstat) with the calculation based on individually fitted rate constants (MRdyn) revealed a very close correlation in spite of a moderate systematic difference in absolute values.
Similar content being viewed by others
References
Warburg O: On the origin of cancer cells. Science 123: 309–314, 1956
Cummins CJ, Smith BH, Kornblith PL: Biochemistry of brain tumors. In: Wilkins RH, Rengachary SS (eds) Neurosurgery, Vol 1. McGraw Hill, New York 535–538, 1985
iChiro G: Positron emission tomography using (18F)fluorodeoxyglucose in brain tumors — a powerful diagnostic and prognostic tool. Invest Radiol 22: 360–371, 1987
Eigenbrodt E, Fister P, Reinacher M: New perspectives on carbohydrate metabolism in tumor cells. In: Beitner R (ed) Regulation of Carbohydrate Metabolism. CRC Press, Boca Raton, 1985
Flier JS: Elevated levels of glucose transport and transporter messenger-RNA are induced by ras or src oncogenes. Science 235: 1492–1495, 1987
Sokoloff L, Reivich M, Kennedy C, DesRosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M: The (14C)-deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916, 1977
Hawkins RA, Phelps ME, Huang SC: Effects of temporal-sampling, glucose metabolic rates and distribution of the blood-brain barrier on the FDG model with and without a vascular compartment: studies in human brain tumors with PET. J Cereb Blood Flow Metab 6: 170–183, 1986
Gjedde A, Wienhard K, Heiss WD, Kloster G, Diemer NH, Herholz K, Pawlik G: Comparative regional analysis of 2-fluorodeoxyglucose and methylglucose uptake in brain of four stroke patients. With special reference to the regional estimation of the lumped constant. J Cereb Blood Flow Metab 5: 163–178, 1985
Kapoor R, Spence AM, Muzi M, Graham MM, Abbott GL, Krohn KA: Determination of the deoxyglucose and glucose phosphorylation ratio and the lumped-constant in rat-brain and a transplantable rat glioma. J Neurochem 53: 37–44, 1989
Herholz K, Ziffling P, Staffen W, Pawlik G, Wagner R, Wienhard K, Heiss WD: Uncoupling of hexose transport and phosphorylation in human gliomas demonstrated by PET. Eur J Cancer Clin Oncol 24: 1139–1150, 1988
Zülch KJ: Histology Typing of Tumors of the Central-Nervous-System. Geneva: World Health Organization, 1979
Herholz K: Nonstationary spatial filtering and accelerated curve fitting for parametric imaging with dynamic PET. Eur J Nucl Med 14: 477–484, 1988
Herholz K, Pawlik G, Wienhard K, Heiss WD: Computer assisted mapping in quantitative analysis of cerebral positron emission tomograms. J Comput Assist Tomogr 9: 154–161, 1985
Wienhard K, Pawlik G, Herholz K, Wagner R, Heiss WD: Estimation of local cerebral glucose utilization by positron emission tomography of (18F)2-fluoro-2-deoxy-D-glucose: A critical appraisal of optimization procedures. J Cereb Blood Flow Metab 5: 115–125, 1985
Herholz K, Wienhard K, Pietrzyk U, Pawlik G, Heiss WD: Measurement of blood-brain hexose transport with dynamic PET: comparison of 18F-2-fluoro-2-deoxyglucose and 11CO-methylglucose. J Cereb Blood Flow Metab 9: 104–110, 1989
Nakada T, Kwee IL: Heterogeneity of regional cerebral glucose metabolism demonstrated in situ in rat brain by 19F NMR rotating frame zeugmatography: one dimensional chemical shift imaging of normal and gliosarcoma implanted brain. Magn Reson Imag 5: 259–266, 1987
Loreck DJ, Cummins CJ, Galarraga J, Phang JM: Regulation of the pentose-phosphate-pathway in human astrocytes and gliomas. Metab Brain Dis 2: 31–46, 1987
Nelson T, Lucignani G, Atlas S, Crane AM, Dienel CA, Sokoloff L: Reexamination of glucose-6-phosphatase activity in the brain in vivo: no evidence for a futile cycle. Science 229: 60–62, 1985
Huang MT, Veech RL: Metabolic fluxes between (14C)2-deoxy-D-glucose and (14C)2-deoxy-D-glucose 6-phosphate in brain in vivo. J Neurochem 44: 567–573, 1985
Graham MM, Spence AM, Muzi M, Abbott GL: Deoxyglucose kinetics in a rat brain tumor. J Cereb Blood Flow Metab 9: 315–322, 1989
Iida H, Kanno I, Miur S, Murakami M, Takahashi K, Uemura K: Error analysis of a quantitative cerebral blood flow measurement using H2 150 autoradiography and positron emission tomography, with respect to the dispersion of the input function. J Cereb Blood Flow Metab 6: 536–545, 1986
Bustamante E, Morris HP, Pedersen PL: Energy metabolism of tumor cells. J Biol Chem 256: 8699–8704, 1981
Graham JF, Cummins CJ, Smith BH, Kornblith PL: Regulation of hexokinase in cultured gliomas. Neurosurgery 17: 537–542, 1985
Patronas NJ, DiChiro G, Kufta C, Bairamian D, Kornblith PL, Simon R, Larson SM: Prediction of survival in glioma patients by means of positron emission tomography. J Neurosurg 62: 816–822, 1985
Alavi JB, Alavi A, Chawluk J, Kushner M, Powe J, Hickey W, Reivich M: Positron emission tomography in patients with glioma — a predictor of prognosis. Cancer 62: 1074–1078, 1988
Luyten PR, Ad Marien JH, Heindel W, van Gerwen PHJ, Herholz K, den Hollander JA, Friedmann G, Heiss WD: Metabolic imaging of patients with intracranial tumors: H-1 MR spectroscopic imaging and PET. Radiology 176: 791–799, 1990
Lammertsma AA, Brooks DJ, Frackowiak RSJ, Beaney RP, Herold S, Heather JD, Palmer AJ, Jones T: Measurement of glucose utilisation with (18F)2-fluoro-2-deoxy-D-glucose: A comparison of different analytical methods. J Cereb Blood Flow Metab 7: 161–172, 1987
Kim CK, Alavi JB, Alavi A, Reivich M: New grading system of cerebral gliomas using positron emission tomography with F-18-fluorodeoxyglucose. J Neuro-Oncology 10: 85–91, 1991
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Herholz, K., Rudolf, J. & Heiss, WD. FDG transport and phosphorylation in human gliomas measured with dynamic PET. J Neuro-Oncol 12, 159–165 (1992). https://doi.org/10.1007/BF00172667
Issue Date:
DOI: https://doi.org/10.1007/BF00172667