Association of FDG uptake and kinetics with apoptosis related gene expression

1764 Objectives: Apoptosis is associated with tumor growth and progression in many neoplasms. This study was performed to assess the impact of apoptosis related gene expression on FDG kinetics and uptake in colorectal tumors. Methods: PET examinations with 18F-FDG were performed in 21 patients with primary colorectal tumors. Tracer kinetics was measured using a multi-frame protocol (60 min following tracer injection). A two-tissue compartment and a non compartment model were used to assess the tracer kinetics quantitatively. Furthermore, SUV (55-60 minutes) and FDG influx were calculated. Following surgery, tumor specimen were evaluated for apoptosis related gene expression using gene array technology. The volumes-of-interest (VOI) used for the quantitative evaluation of the PET data were adjusted according to the area where the tissue specimen was removed in order to match PET and apoptosis related gene expression data. Results: Overall tracer uptake, as measured by SUV, as well as tracer kinetics, evaluated by the models, were generally enhanced and highly variable in the tumors. Negative regression functions and correlations existed for k1 (r=-0.45), fractal dimension (FD) (r=-0.55), influx (r=-0.51), and SUV (r=-0.39), when PET results were compared to bcl-2 expression data. It is well known that bcl-2 is inhibiting apoptosis, therefore increased apoptosis can be expected with higher values for k1, FD, influx, and SUV. Tumors frequently show mutations of p53, which we also observed in the colorectal neoplasms. One p53 mutation, also associated with the Li-Fraumeni syndrome, was positively correlated with FD, influx, and SUV. Again, the results direct to enhanced apoptosis with higher values for these PET parameters. Interestingly, the cdk inhibitor p21 binding protein, a protein that prevents phosphorylation of cyclin-dependent kinases and mediates p53 suppression of tumor cell growth, was positively correlated with k1 (r=0.55), while the p21 protein activator was negatively correlated with k3. The data suggest a higher effect of cell cycle suppression (followed by enhanced apoptosis) with high k1 (FDG transport) and low k3 (FDG phosphorylation). Conclusions: The results direct to a modulation of the FDG influx and kinetics by apoptosis related gene expression. Low apoptosis is reported to be associated with enhanced tumor growth and more likely in patients with poor prognosis. Based on the results, the quantitative assessment of FDG uptake and kinetics can help to select patients with primary colorectal tumors and poor prognosis.