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

Abstract

BackgroundNon-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.MethodsCollagen-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.ResultsQuantification 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.ConclusionThese 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.

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…The main limitation of 19 F cell tracking is its relatively low sensitivity when compared to cellular imaging with iron nanoparticles. In this paper, we compare 19 F-and ironbased methods for MSC tracking in vivo.…”

“…In this paper, we compare 19 F-and ironbased methods for MSC tracking in vivo. Our specific goals were: 1) to evaluate the use of a balanced steady-state free precession (bSSFP) sequence for 19 F cell tracking; 2) to demonstrate that primary human MSC (hMSC) could be labeled with a sufficient quantity of the 19 F agent, Cell Sense, to allow for cell detection, without altering cell viability or differentiation; and 3) to compare the information obtained from imaging iron-and 19 F-labeled hMSC after intramuscular (IM) injection in healthy mice.…”

“…12 One of the key advantages of these agents is the very high specificity; since this atom is mainly absent from the body, there is no background 19 F signal in MR images. In addition, the fluorine signal can be accurately quantified from the MR images by comparing the 19 F signal in the tissue of interest to an external reference containing a known amount of fluorine atoms. Finally, unlike iron nanoparticles, perfluorocarbon nanoemulsions are biologically inert.…”

“…Examples of 19 F MR imaging performed to date include: monitoring inflammation (tumor models, rheumatoid arthritis, lung injuries, and after ischemia in the lung or brain), [16][17][18][19] detection of T cell and dendritic cell migration, 20,21 and tracking the fate of transplanted hematopoietic and neural stem cells.…”

Cell-Based Therapeutic Strategies in Multiple Sclerosis

“…[84][85][86] Additionally, in vivo perfluorocarbon emulsion infusion followed by 19 F MRI has been shown to preferentially detect areas of inflammation both in the CNS and systemically via preferential uptake by CD68+ macrophages, providing a non-invasive measure of disease activity in murine models of inflammatory disease. [87][88][89][90] Thus, the advantage of these labelling modalities includes the ability to directly visualise (and potentially in an EAE mouse model in which human MSCs engineered to express a myelin oligodendrocyte glycoprotein-specific receptor were intranasally delivered and found to significantly improve EAE symptoms better than non-engineered human MSCs, and prevented further EAE induction. 93 Indeed, while MSCs are a promising therapeutic resource, other stem cell sources may supplant MSCs in the future.…”