FDG accumulation and tumor biology.

The tumoral uptake of fluorine-18-deoxyglucose (FDG) is based upon enhanced glycolysis. Following injection, FDG is phosphorylated and trapped intracellularly. An important mechanism to transport FDG into the transformed cell is based upon the action of glucose transporter proteins; furthermore, highly active hexokinase bound to tumor mitochondria helps to trap FDG into the cell. In addition, enhanced FDG uptake may be due to relative hypoxia in tumor masses, which activates the anaerobic glycolytic pathway. In spite of these processes, FDG uptake is relatively aspecific since all living cells need glucose. Clinical use is therefore recommended in carefully selected patients.

[1]  Y. Yazaki,et al.  Characterization of rat GLUT5 and functional analysis of chimeric proteins of GLUT1 glucose transporter and GLUT5 fructose transporter. , 1995, Endocrinology.

[2]  John Calvin Reed,et al.  Anchorage dependence, integrins, and apoptosis , 1994, Cell.

[3]  C. D. Arnett,et al.  Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  M Hatanaka,et al.  Transport of sugars in tumor cell membranes. , 1974, Biochimica et biophysica acta.

[5]  H. Lodish,et al.  Sequence and structure of a human glucose transporter. , 1985, Science.

[6]  M. Birnbaum,et al.  Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription. , 1987, Science.

[7]  N. Alpert,et al.  FDG-PET in oncology: there's more to it than looking at pictures. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[9]  J S Fowler,et al.  A FLUORINATED GLUCOSE ANALOG, 2‐FLUORO-2‐DEOXY-D‐GLUCOSE (F‐18): NONTOXIC TRACER FOR RAPID TUMOR DETECTION , 1980, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  G. Weber.  Enzymology of cancer cells (second of two parts). , 1977, The New England journal of medicine.

[11]  R. Wahl,et al.  Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. , 1996, Nuclear medicine and biology.

[12]  P. Pedersen,et al.  Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. , 1981, The Journal of biological chemistry.

[13]  E. Hoffman,et al.  Tomographic measurement of local cerebral glucose metabolic rate in humans with (F‐18)2‐fluoro‐2‐deoxy‐D‐glucose: Validation of method , 1979, Annals of neurology.

[14]  A. Carruthers,et al.  Facilitated diffusion of glucose. , 1990, Physiological reviews.

[15]  G I Bell,et al.  Structure and function of mammalian facilitative sugar transporters. , 1993, The Journal of biological chemistry.

[16]  P. Pedersen,et al.  Glucose phosphorylation in tumor cells. Cloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase. , 1990, The Journal of biological chemistry.

[17]  M. Mueckler,et al.  Homeostasis without a GLUT , 1995, Nature.

[18]  M. Tang,et al.  Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53 , 1996, Science.

[19]  L M Hamberg,et al.  The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  S. Baldwin,et al.  Trafficking of glucose transporters-signals and mechanisms , 1995, Bioscience reports.

[21]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[22]  G. Weber.  Enzymology of cancer cells (first of two parts). , 1977, The New England journal of medicine.

[23]  Y. Ebina,et al.  Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. , 1992, The Journal of biological chemistry.

[24]  N. K. Monakhov,et al.  Physicochemical properties and isoenzyme composition of hexokinase from normal and malignant human tissues. , 1978, Journal of the National Cancer Institute.

[25]  A Carruthers,et al.  Human erythrocyte sugar transport is incompatible with available carrier models. , 1996, Biochemistry.

[26]  R. Shigemoto,et al.  Distribution of the glucose transporters in human brain tumors. , 1992, Cancer research.

[27]  E. Hoffman,et al.  TOMOGRAPHIC MEASUREMENT OF LOCAL CEREBRAL GLUCOSE METABOLIC RATE IN HUMANS WITH (F‐18)2‐FLUORO-2‐DEOXY-D‐GLUCOSE: VALIDATION OF METHOD , 1980, Annals of neurology.

[28]  H. Amos,et al.  Enhancement of hexose entry into chick fibroblasts by starvation: differential effect on galactose and glucose. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[29]  L. Freeman,et al.  Nuclear medicine annual. , 1982 .

[30]  H. Lodish,et al.  Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. , 1987, Science.

[31]  T Ido,et al.  Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  A. Wolf,et al.  Metabolic trapping as a principle of oradiopharmaceutical design: some factors resposible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose. , 1978, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  Frank McCormick,et al.  The GTPase superfamily: a conserved switch for diverse cell functions , 1990, Nature.

[34]  L. Sokoloff,et al.  Influence of Plasma Glucose Concentration on Lumped Constant of the Deoxyglucose Method: Effects of Hyperglycemia in the Rat , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  G. Lienhard,et al.  Kinetics of the purified glucose transporter. Direct measurement of the rates of interconversion of transporter conformers. , 1989, Biochemistry.

[36]  R L Wahl,et al.  Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. , 1991, Radiology.

[37]  Scott T. Grafton,et al.  PET and [18F]-FDG in oncology: a clinical update. , 1996, Nuclear medicine and biology.

[38]  K. McKenzie,et al.  Frequent p53 gene mutations and novel alleles in familial breast cancer. , 1994, Cancer research.

[39]  J S Fowler,et al.  Increased accumulation of 2-deoxy-2-[18F]Fluoro-D-glucose in liver metastases from colon carcinoma. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[40]  J. Ruhlmann,et al.  Fdg-pet in clinical oncology: review and evaluation of results of a private clinical pet center , 1998 .

[41]  O. Warburg.  On the origin of cancer cells. , 1956, Science.

[42]  M. Birnbaum,et al.  Growth factors rapidly induce expression of the glucose transporter gene. , 1988, The Journal of biological chemistry.

[43]  A. Floridi,et al.  Effect of lonidamine on the mitochondrial potential in situ in Ehrlich ascites tumor cells. , 1996, Anticancer research.

[44]  J. Marsh,et al.  The GTPase superfamily , 1993 .

[45]  W. Kabsch,et al.  The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. , 1997, Science.

[46]  D. Bentley,et al.  Identification of the breast cancer susceptibility gene BRCA2 , 1995, Nature.

[47]  R. G. Manning,et al.  Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain. , 1982, Radiology.

[48]  Kazutomo Inoue,et al.  Over-expression of facilitative glucose transporter genes in human cancer. , 1990, Biochemical and biophysical research communications.

[49]  G. van Kaick,et al.  PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[50]  G. T. Budd,et al.  Estrogen receptor mutations in tamoxifen-resistant breast cancer. , 1994, Cancer research.

[51]  C. Chi,et al.  Elevation of facilitated glucose‐transporter messenger RNA in human hepatocellular carcinoma , 1990, Hepatology.

[52]  G Lucignani,et al.  Fluorine-18-fluorodeoxyglucose PET to determine regional cerebral glucose utilization: a re-examination. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.