Review Article
FDG Accumulation and Tumor Biology

https://doi.org/10.1016/S0969-8051(97)00226-6Get rights and content

Abstract

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.

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.

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