Factors Influencing [F-18] 2-Fluoro-2-Deoxy-d-Glucose (F-18 FDG) Uptake in Melanoma Cells: The Role of Proliferation Rate, Viability, Glucose Transporter Expression and Hexokinase Activity

Abstract

Using human (SK-MEL 23, SK-MEL 24 and G361) and murine (B16) melanoma cell lines, the coregulatory potential of the uptake of the positron emission tomography (PET) tracer, [Fluorine-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) has been investigated in relationship to tumor characteristics. Comparative studies among the four melanoma cell lines demonstrated that the lowest FDG uptake in SK-MEL 24 corresponded strongly to the data for DT (population doubling time) and MTT (tetrazolium salt) cell viability as well as hexokinase (HK) activity, but was not related to the glucose transporter 1 (GLUT 1) expression level. Furthermore, the FDG uptake in each melanoma cell line measured by cell cycle kinetics was significantly positively correlated to both the proliferation index (PI=S/G2M phase fractions) and the cell viability, though with one exception relating to the PI of the lowest FDG uptake cell line, SK-MEL 24. No positive correlation was found between the expression of GLUT 1 and FDG uptake in any individual cell line. However, the HK activities in SK-MEL 23 and 24 showed considerable positive relationships with FDG uptake. Our present study suggests that both the proliferation rate and the cell viability of melanoma cells may be key factors for FDG uptake and that HK activity, rather than GLUT 1 expression, seems to be a major factor.

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

“…To determine the hypothesis, the HK activity was investigated. It was observed that BMEC grown in higher glucose concentrations (5, 10 and 20 mM) had higher HK activities, which confirmed the previous assumption and agreed with Yamada et al (2005), who reported that HK activities showed positive relationship with glucose uptake. As both HK1 and HK2 were expressed in lactating rat mammary gland (Kaselonis et al, 1999), and it is interesting to define the specific role each HK played in the BMEC, the expression of HK1 mRNA could not be detected, whereas the HK2 was expressed at a relatively high level in the BMEC.…”

Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

“…Measurement of FDG uptake in tumors may not only assist in oncologic imaging, but can also be useful in the evaluation of the treatment effect of anti-glycolytic agents [23]. Several studies showed that FDG may be used to study drug effects in vitro [24,25]. Our study further validated this principle in vivo, by showing lesser FDG uptake after 3-BrPA treatment, which was specific for tumor tissue.…”

Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines

“…Glucose uptake in our study was over-expressed in transformed cells compared to normal thyrocytes but the degree of over-expression did not correlate to the degree of GLUT-1 expression. Again, these findings are not specific for thyrocytes: GLUT-1 expression was increased in more malignant prostate carcinoma cell lines [21] and inhibition of GLUT-1 reduced proliferation and increased apoptosis in breast and lung cancer cell lines [22]; in melanoma cell lines proliferation correlated to glucose uptake but not to GLUT-1 expression [23]. Also in vivo GLUT-1 expression did not correlate to glucose uptake and proliferation [24].…”