Review ArticleFDG Accumulation and Tumor Biology
Introduction
Fluorine-18 deoxyglucose (FDG) is used by many centers for tumor imaging and assessment of the metabolic state of malignant lesions. There is ample evidence that the accumulation of FDG is based on enhanced glycolysis, which has often been associated with the growth rate and the malignancy potential of the tumor. Although many patients have benefited from scintigraphy with FDG, one should be aware of the diagnostic limitations associated with the use of this tracer. A greater understanding of this behaviour not only serves a scientific goal but it also helps to understand scintigraphic patterns observed under clinical circumstances in a better way.
To this end, this article reviews two major aspects of FDG-scintigraphy: First, it provides an overview of tumor biology associated with glucose metabolism; second, it relates the relevant biological facts to characteristics of FDG in clinical tumor-scanning.
Section snippets
On the Origin of Cancer
How cancer arises is no longer a secret. According to modern insights, a tumor consists of cells in which a transformation has taken place owing to exposure to environmental factors, which may cause damage or alteration of the cellular DNA. Such factors include viruses, bacteria, parasites, a variety of chemicals and both ultraviolet and ionizing radiation. Among these carcinogenic agents, two important types have been recognized. First are those agents that damage genes or parts of genes that
Glucose Uptake in Tumor Cells
Glucose assumes a central role among the fuels for cellular energy metabolism. Warburg was among the first to demonstrate that tumor cells have an altered glucose metabolism [48]. Even under aerobic conditions these cells showed a high excretion of lactic acid. It was therefore concluded that the energy production of tumor cells occurs via two mechanisms: both the degradation of glucose to lactic acid and the oxidation of glucose [49]. This increased glucose metabolism was primarily thought to
Trapping and Metabolism of Glucose and Deoxyglucose
When glucose enters the living cell, phosphorylation catalyzed by hexokinase occurs. The resulting molecule glucose-6-phosphate may enter further metabolic pathways. Glucose-6-phosphate inhibits hexokinase in an allosterical way, so that the uptake of glucose by cells is dependent on the rate by which glucose-6-phosphate is metabolized. The enzyme glucose-6-phosphate isomerase transfers glucose-6-phosphate into fructose-6-phosphate. This isomerization converts the aldose into a ketone through a
FDG Uptake in Relation to Pathophysiology
Local cerebral glucose consumption was measured by Sokoloff et al. [43]in 1977 using carbon-14-labelled deoxyglucose in rat. One year later Gallagher et al. [18]reported on the use of 18F-2-deoxy-2-fluoroglucose (FDG) to study overall glucose metabolism in rodents. Soon after that, tumor detection in animals with FDG was achieved by Som et al. [44]. The scintigraphic visualization of liver metastases in patients was described by Yonekura et al. [54], and Patronas et al. [34]reported on FDG
Concluding Remarks
Although a large number of articles have appeared on the clinical use of FDG, only a few have paid attention to biological factors influencing the uptake of this radiopharmaceutical 8, 16, 45. There is no doubt that with increasing cellular transformation, the malignant cell demands more glucose, and its requirements can be met by the upregulation of the membrane glucose transporter proteins. Also, the activation of enzymes involved in glucose metabolism and the deletion of nonrelevant enzymes
Acknowledgements
The authors are grateful to Ms. Tilly Hagendoorn for excellent secretarial assistance and to Dr. Tarek Abdelfatah el-Maghraby for supplying Fig. 1. This work was supported by a grant of Le Ministère de l’Education Nationale, de l’Enseignement Supérieure et de la Recherche to E.K.J.P. under reference number DRIC/MDLM/MT 1701.
References (54)
- et al.
Glucose phosphorylation in tumor cellsCloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase
J. Biol. Chem.
(1990) - et al.
Structure and function of mammalian facilitative sugar transporters
J. Biol. Chem.
(1993) - et al.
Energy metabolism of tumor cellsRequirement for a form of hexokinase with a propensity for mitochondrial binding
J. Biol. Chem.
(1981) - et al.
PET and [18F]-FDG in oncologyA clinical update
Nucl. Med. Biol.
(1996) - et al.
WAF1, a potential mediator of p53 tumor suppression
Cell
(1993) Transport of sugars in tumor cell membranes
Biochim. Biophys. Acta
(1974)- et al.
Growth factors rapidly induce expression of the glucose transporter gene
J. Biol. Chem.
(1988) - et al.
Influence of hypoxia on tracer accumulation in squamous cell carcinomaIn vitro evaluation for PET imaging
Nucl. Med. Biol.
(1996) - et al.
Type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes
J. Biol. Chem.
(1992) - et al.
Anchorage dependence, integrins and apoptosis
Cell
(1994)
Over-expression of facilitative glucose transporter genes in human cancer
Biochem. Biophys. Res. Commun.
Kinetics of the purified glucose transporterDirect measurement of the rates of interconversion of transporter conformers
Biochemistry
Trafficking of glucose transporters—signals and mechanisms
Biosci. Rep.
FDG-PET in clinical oncologyReview and evaluation of results of a private clinical PET center
Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription
Science
The GTPase superfamilyA conserved switch for diverse cell functions
Nature
Does fluorine-18 fluorodeoxyglucose metabolic imaging of tumours benefit oncology?
Eur. J. Nucl. Med.
Facilitated diffusion of glucose
Physiol. Rev.
Human erythrocyte sugar transport is incompatible with available carrier models
Biochemistry
Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hot spots in p53
Science
Glycolysis and growth rate in normal and in hexokinase transfected NIH 3T3 cells
Oncol. Res.
FDG-PET in oncologyThere’s more to it than looking at pictures
J. Nucl. Med.
Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes
Science
Metabolic trapping as a principle of radiopharmaceutical designSome factors responsible for the biodistribution of [18-F] 2-deoxy-2-fluoro-d-glucose
J. Nucl. Med.
Frequent p53 gene mutations and novel alleles in familial breast cancer
Cancer Res.
PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy
J. Nucl. Med.
The dose uptake ratio as an index of glucose metabolismUseful parameter or oversimplification?
J. Nucl. Med.
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