Department of Research and Development, Celsense, Inc,, Pittsburgh, PA 15222, USA.
J Inflamm (Lond). 2012 Jun 21;9(1):24. doi: 10.1186/1476-9255-9-24.
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.
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.
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.
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.
迫切需要非侵入性成像来测量炎症的进展,以评估自身免疫性疾病(如类风湿关节炎)的进展,并监测治疗反应。V-Sense 是一种全氟碳(PFC)造影剂,它优先标记炎症细胞,然后将这些细胞从全身循环招募到炎症部位,通过 19F MRI 进行检测。由于宿主中没有 19F 背景,因此检测具有高度特异性,可以作为存在炎症程度的替代生物标志物。
胶原诱导的关节炎大鼠模型与人 RA 具有许多相似之处,用于研究 PFC 造影剂在一段时间内通过 19F MRI 显示炎症积累的能力。通过卡尺测量和第 15、22 和 29 天的 19F MRI 监测大鼠后肢疾病的进展,包括临床症状疾病的高度。以正常大鼠作为对照。研究了在接受口服泼尼松龙治疗的大鼠队列中,PFC 造影剂和 19F MRI 评估治疗效果的能力。
MRI 测量的受影响肢体的 19F 信号的定量与疾病严重程度呈线性相关。在疾病进展的动物中,19F 信号的增加反映了炎症细胞不断向该部位募集,而在接受治疗的动物中则没有观察到 19F 信号的增加,这些动物的疾病得到了临床缓解。
这些结果表明,19F MRI 可用于定量和定性评估治疗方案的纵向反应,同时还可以揭示参与炎症过程的单核细胞向解剖部位的募集。这项研究可能支持使用 19F MRI 临床定量和监测炎症的严重程度,并评估 RA 和其他具有炎症成分的疾病的治疗效果。