Assessment of acute bone loading in humans using [${}^{18}$F]NaF PET/MRI

The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [${}^{18}$F]-sodium fluoride ([${}^{18}$F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading. Twelve healthy subjects underwent two consecutive 50-min [${}^{18}$F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of K${}_i$${}^{NLR}$, K${}_1$, k${}_2$, k${}_3$, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUV${}_{max}$ were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone. Exercise induced a significant (p < <0.001) increase in [${}^{18}$F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K${}_1$ and blood volume) increased, whereas the NaF extraction fraction [k${}_3$/(k${}_2$ + k${}_3$)] was reduced. Bone loading induces an acute response in bone physiology as quantified by [${}^{18}$F]NaF PET kinetics. Dynamic imaging after bone loading using [${}^{18}$F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.