Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer

Abstract

This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET) imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic (18)F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by (18)F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

Figure 1

Cross-sectional PET images of tumor-bearing rats taken 40 minutes following intravenous administration of FDG. Rats are in the supine position and the level of cross section is at the upper thorax. Xenografts (arrows) are located on the superior anterior chest wall at the base of the neck. Areas of brightness represent regions of greater [¹⁸F]FDG concentration. (A) Rat bearing two representative C85 human colorectal xenografts. (B) Rat bearing two representative C29 human colorectal xenografts.

Figure 2

Average time-activity curves of [¹⁸F]FDG accumulation in five human colorectal xenografts. Data points represent then mean (±SD) for each set of xenografts.

Figure 3

Comparison of maximum SUVs of five human colorectal xenografts. Open circles represent individual SUV values and closed circles represent the mean (±SD) for each set of values. Significance differences between groups of xenografts is indicated by (*).

Figure 4

Correlation of maximum SUV (mean±SEM) with the activity of hexokinase (mean±SEM) in five human colorectal xenografts. Each xenograft is represented by a filled circle.

Figure 5

The relationship between tumor doubling time, maximum SUV, and hexokinase. SUV_max (mean±SEM) for each colorectal xenograft (open circles), and the activity of hexokinase (mean±SEM) for each colorectal xenograft (filled circles) are both correlated to the tumor doubling time.