Preclinical dynamic 18F-FDG PET - tumor characterization and radiotherapy response assessment by kinetic compartment analysis

Background. Non-invasive visualization of tumor biological and molecular processes of importance to diagnosis and treatment response is likely to be critical in individualized cancer therapy. Since conventional static F-18-FDG PET with calculation of the semi-quantitative parameter standardized uptake value (SUV) may be subject to many sources of variability, we here present an approach of quantifying the F-18-FDG uptake by analytic two-tissue compartment modeling, extracting kinetic tumor parameters from dynamic F-18-FDG PET. Further, we evaluate the potential of such parameters in radiotherapy response assessment. Material and methods. Male, athymic mice with prostate carcinoma xenografts were subjected to dynamic PET either untreated (n=8) or 24 h post-irradiation (7.5 Gy single dose, n=8). After 10 h of fasting, intravenous bolus injections of 10 15 MBq F-18-FDG were administered and a 1 h dynamic PET scan was performed. 4D emission data were reconstructed using OSEM-MAP, before remote post-processing. Individual arterial input functions were extracted from the image series. Subsequently, tumor F-18-FDG uptake was fitted voxel-by-voxel to a compartment model, producing kinetic parameter maps. Results. The kinetic model separated the F-18-FDG uptake into free and bound tracer and quantified three parameters; forward tracer diffusion (k(1)), backward tracer diffusion (k(2)), and rate of F-18-FDG phosphorylation, i.e. the glucose metabolism (k(3)). The fitted kinetic model gave a goodness of fit (r(2)) to the observed data ranging from 0.91 to 0.99, and produced parametrical images of all tumors included in the study. Untreated tumors showed homogeneous intra-group median values of all three parameters (k(1), k(2) and k(3)), whereas the parameters significantly increased in the tumors irradiated 24 h prior to F-18-FDG PET. Conclusions. This study demonstrates the feasibility of a two-tissue compartment kinetic analysis of dynamic F-18-FDG PET images. If validated, extracted parametrical maps might contribute to tumor biological characterization and radiotherapy response assessment.