¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Abstract

It is hoped that in the not too distant future, noninvasive imagingbased molecular interrogation and characterization of tumors can improve our fundamental understanding of the dynamic biologic behavior of cancer. For example, the new dimension of diagnostic information that is provided by 18 F-FDG PET has led to improved clinical decision making and management changes in a substantial number of patients with cancer. In this context, the aim of this review is to bring together and summarize the current data on the correlation between the underlying molecular biology and the clinical observations of tumor 18 F-FDG accumulation in 3 major human cancers: lung, breast, and colon.Key Words: molecular biology; molecular imaging; oncology; PET; PET/CT; breast cancer; colon cancer; 18 F-FDG; lung cancer Theemergenceoft he central role of PET with 18 F-FDG for the imaging evaluation of patients with cancer is undeniable. The development of hybrid PET/CT systems, regional distribution centers for 18 F-FDG, rapidly accumulating clinical experience, and improved reimbursement have all contributed to this phenomenal success. 18 F-FDG PET has been used for diagnosis, initial staging, restaging, prediction, and monitoring of treatment response, surveillance, and prognostication in a variety of cancers. The new dimension of diagnostic information that is provided by 18 F-FDG PET has also led to improved clinical decision making and management changes in a substantial number of patients (1-3).18 F-FDG PET is a molecular imaging technique that monitors tissue glucose metabolism. It has long been known that most tumors are hypermetabolic, with increased glucose metabolism (Warburg effect). The underlying mechanism and reason for elevated glucose metabolism in cancers is multifactorial and more complex than it may appear at first glance (4). These factors include but are not limited to tumor-related components (e.g., type and histologic differentiation), biochemical and molecular alterations (e.g., glucose metabolic pathway, hypoxia), and nontumor-related constituents (e.g., inflammation) (5-8). The 2 recent excellent reviews by Gillies et al. and Plathow et al. summarized the current understanding of the phenotype of elevated glucose metabolism in cancers (9,10). In simple terms, it was postulated that the relationship between tumor growth and glucose metabolism may be explained in terms of adaptation to hypoxia through upregulation of glucose transporters (GLUTs) and translocation and increased enzymatic activity of hexokinase. However, energy production by glycolysis is relatively inefficient (2 adenosine triphosphates produced per glucose with glycolysis rather than 30 ATPs produced with complete oxidation) and produces a toxic acidic microenvironment (9,10). It has been proposed that the increased extracellular acid production may be the underlying basis for promoting tumor survival and spread in the context of the 6 hallmarks of cancer-self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apopt...

Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma: Correlation with Glucose Transporters and p53 Expression

“…The GLUT12 expression levels are very expressive in all cell lines, which is in agreement with the data presented by other studies indicating that this transporter has an active role in [ 18 F]FDG uptake in other tumors. 7 So it seems that also in HCC the GLUT12 may have a fairly active role in the transport of this radiopharmaceutical. Although the GLUT2 was described as the glucose transporter that is more expressed in normal hepatocytes, 15 our study indicates that this transporter doesn't have major influence on [ 18 F]FDG uptake in HCC cell lines studied, considering that in these cell lines, among the GLUTs studied, the GLUT2 expression levels are little relevant.…”

“…[ 18 F]FDG PET has been used for diagnosis, initial staging, restaging, course, and monitoring of treatment response, surveillance, and prognosis in a variety of cancers. 7 Although this imaging technique is not widely used for liver tumors, recent studies have shown that PET enables the identification of different uptake profiles in tumors of the same organ, namely HCC, but with different genetic profiles, which indicates that PET can be used in the diagnosis of liver cancers, leading the patients to a more personalized therapies. [8][9][10] Increased [ 18 11,12 GLUT1 and GLUT3 were originally identified as glucose transporters with primary role in the transport of [ 18 F] FDG, since it is known that these transporters are overexpressed in tumor cells.…”

“…However, more recently, GLUT5 and GLUT12 also appeared as transporters with an active role in this process, in particular in breast cancer cells. 7,13,14 GLUT2 is a transporter fairly expressed in normal liver which may play a significant role in HCC. 15 16,17 Thus, the objective of this experimental work was to establish the [ 18 F]FDG uptake profile of three HCC human cell lines and correlate them with the expression levels of p53, GLUT1, GLUT2, GLUT3, GLUT5 and GLUT12.…”

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

“…This technique is useful in the diagnosis and prognosis of breast cancer, especially regarding the detection of distant metastases, and recurrent disease as well as in monitoring response to therapy (Jadvar et al 2009). This increased uptake of glucose, especially through glucose transporter 1 (GLUT1), is a consequence of an increased glycolytic metabolism that generates acids inside the cell.…”

Cancer Cell Metabolism

“…Supplying cancers with radioactive glucose derivatives allows them to be examined using 18 fluorodeoxyglucose -positron emission tomography (FDG-PET). Indeed, the tools used to determine the nature of the Warburg effect have demonstrated the clinical importance of glycolysis in cancer cell metabolism (Gambhir et al 2001;Czernin and Phelps 2002;Gambhir 2002;Jadvar et al 2009). Consequently, several emerging therapeutic approaches have been designed to inhibit tumor cell glycolysis, ranging from the use of nonmetabolizable glucose analogs to blocking critical steps in the pathway, such as those catalyzed by lactate dehydrogenase (LDH), hexokinase-2 (HK2), or the monocarboxylate transporters (MCT) that export lactate to the external microenvironment (Fantin et al 2006;Le et al 2010;Wolf et al 2011).…”