Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (¹⁹F MRI)

<p>Abstract</p> <p>Background</p> <p>Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by ¹⁹F MRI. With no ¹⁹F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present.</p> <p>Methods</p> <p>Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using ¹⁹F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and ¹⁹F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and ¹⁹F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28.</p> <p>Results</p> <p>Quantification of ¹⁹F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in ¹⁹F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in ¹⁹F signal was observed in animals receiving treatment which resulted in clinical resolution of disease.</p> <p>Conclusion</p> <p>These results indicate that ¹⁹F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of ¹⁹F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.</p