18F-Fluoride positron emission tomography/computed tomography for non-invasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis (Arthritis Research & Therapy)

IntroductionEvaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A non-invasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research, for staging of autoimmune disease severity or efficacy of therapeutical intervention. 18F-NaF is a bone seeking tracer well suited for molecular imaging. Therefore, we systematically examined the use of 18F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis for quantification of pathological bone metabolism. Methods: 18F-fluoride was injected in mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints of fore and hind paws was analyzed by PET measurements. For validation of bone metabolism quantified by 18F-fluoride PET, bone surface parameters of high resolution muCT measurements were used. Results: Before clinical arthritis onset, no distinct accumulation of 18F-fluoride was detectable in fore and hind limbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT imaging enabled identification of exact localization of 18F-fluoride signaling in bone or soft tissue. Conclusions: The results from this study suggest that small animal PET/CT using 18F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated non-invasive measurements in vivo allows longitudinal studies monitoring therapeutical intervention.