Evaluation of New Bone Formation in Normal and Osteoporotic Rats with a 3-mm Femur Defect: Functional Assessment with Dynamic PET-CT (dPET-CT) Using 2-Deoxy-2-[18F]Fluoro-d-glucose (18F-FDG) and 18F-Fluoride

Abstract

The aim of the current study was to assess the formation of new bone in a 3-mm created defect in the femur and its adjacent bone tissue in osteoporotic and normal animals. The assessment is based on bone remodeling and glucose metabolism in a rat model with a 3-mm created defct in the femur using (18)F-fluoride and 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) as tracers for dynamic PET-CT (dPET-CT). The (18)F-fluoride PET data were compared with those of (18)F-FDG. Osteoporosis was induced by ovariectomy and a calcium restricted diet in each rat (n = 7). Alternatively, a sham operation was performed in the control group (n = 8). After 3months, all rats were operated to create a 3-mm defect using an oscillating saw in the distal metaphyseal femur, which was internally fixed with a metal plate. Eighteen weeks after osteoporosis induction and 6weeks following femoral surgery, dPET-CT studies scan were performed with (18)F-FDG and (18)F-fluoride. Following PET data acquisition, standardized uptake values (SUVs) were calculated from the tracer concentration values. Then, a two-tissue compartmental learning-machine model was applied to the data for the calculation of the compartment parameters (K1-k4, VB, Ki). Furthermore, a non-compartmental model based on the fractal dimension was applied for quantitative analysis of both groups and both tracers. Finally, multivariate analysis was performed for the statistical analysis of the kinetic data. The values for K1 and Ki were higher in the osteoporotic rats than in the control group. Ki and K1 of (18)F-fluoride in the adjacent bone tissue differ significantly based on the Wilcoxon rank-sum test for the osteoporotic and control group (p < 0.05). The sensitivity and the negative predictive value (NPV) based on linear discriminant analysis was high with a value of 100% for both tracers and both evaluated regions (defect and adjacent bone tissue) when comparing control and osteoporotic rats. The overall accuracy with (18)F-FDG was generally higher than that with (18)F-fluoride for both evaluated regions for the control and osteoporotic rats based on a multiparameter evaluation. In this study, the changes in tracer kinetics accurately discriminated differences in the created defect in the femur and its adjacent bone tissue between osteoporotic and control rats.