Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [15O]H2O and [18F]fluoride ion positron emission tomography

Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [F-18]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K-1 values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The true bone blood flow (f(H2O)) was measured in vertebral bodies by dynamic [O-15]H2O PET, followed by a 120-min dynamic [F-18]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K-1 values (f) and the net uptake of fluoride in bone tissue (K-i), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K-i and k(3) (P<0.05), which was mainly caused by an increase of the fraction of bound tracer in tissue (P<0.01). In contrast, f(H2O),f, the single-pass extraction fraction of [F-18]fluoride (E) and the volume of distribution (DV) of [F-18]fluoride were not significantly different between groups. In both groups, a coupling of the mean f(H2O) and Ki values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [F-18]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [F-18]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease after gastrectomy is mainly related to an up-regulation of the amount of ionic exchange of [F-18]fluoride with the bone matrix, while tracer delivery remains unchanged.