Impact of Cell-Proliferation-Associated Gene Expression on 2-Deoxy-2-[18F]fluoro-d-Glucose (FDG) Kinetics as Measured by Dynamic Positron Emission Tomography (dPET) in Colorectal Tumors
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Glucose transporters and hexokinases determine the kinetics of 2-deoxy-2-[18F]fluoro-d-glucose (FDG). However, the genes controlling these proteins are not independent and may be modulated from other biological processes, e.g., like angiogenesis and proliferation. The impact of cell-proliferation-related genes on the FDG kinetics was assessed in colorectal tumors in this study.
Patients with primary colorectal tumors (n = 25) were examined with positron emission tomography and FDG within 2 days prior to surgery. Tissue specimens were obtained from the colorectal tumor and the normal colon by surgery and gene expression was assessed using gene arrays.
Overall, an increase of the expression of proliferation associated genes was observed by a factor of 2–5.3 for the colorectal tumors as compared with the normal colon. Correlation analysis revealed an impact of cdk2 on K1, thus directing to a modulation of the FDG uptake into the cells. The correlations were generally higher for the FDG influx as compared with the standardized uptake value (SUV). The influx was mainly correlated with proliferation inhibiting genes (cyclin G2, cdk inhibitor 1 C, cdk inhibitor 2B). It was possible to predict the expression of cyclin D2 using a multiple linear regression function and the parameters of the FDG kinetics with r = 0.67. Using a group based analysis it was possible to demonstrate, that tumors with an SUV >12 are associated with a high expression of cyclin D2 in the colorectal tumors. If the gene expression data for cyclin D1, cyclin G2, cdk2, cdk6 and cdk inhibtor 2B were used, the overall FDG uptake as measured by the SUV could be predicted with r = 0.75.
The results suggest that the FDG kinetics is modulated by proliferation associated genes. Especially K1, the parameter for the FDG transport into the cells, is modulated by cdk2. Tumors with a SUV exceeding 12 have usually a higher expression of cyclin D2. The parameters of the FDG kinetics can be used to predict the expression of proliferation associated genes individually.
Key wordsPET FDG Cell cycle Proliferation Gene expression Gene array
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