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

Abstract

Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [¹⁸F]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 [¹⁵O]H₂O PET, followed by a 120-min dynamic [¹⁸F]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 [¹⁸F]fluoride (E) and the volume of distribution (DV) of [¹⁸F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f _H2O and K _i 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 [¹⁸F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [¹⁸F]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 [¹⁸F]fluoride with the bone matrix, while tracer delivery remains unchanged.