Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
J Nucl Cardiol. 2021 Oct;28(5):2346-2357. doi: 10.1007/s12350-020-02044-0. Epub 2020 Feb 3.
MCC950 is a novel NLRP3 inflammasome inhibitor that possesses potent anti-inflammatory properties in acute myocardial infarction (AMI). However, the lack of noninvasive monitoring methods limits its potential clinical translation. Thus, we sought to investigate whether F-FDG PET imaging can monitor the therapeutic effects of MCC950 in an AMI murine model.
C57BL/6 mice were used to generate an AMI model. MCC950 or sterile saline was intraperitoneally administered 1 hour after surgery and then daily for 7 consecutive days. F-FDG PET (inflammation) imaging was used to monitor inflammatory changes on days 3 and 5. Immunohistochemistry and Western blot were used to detect inflammatory markers and to confirm the PET imaging results. F-FDG PET (viability) imaging was used to quantitate the viability defect expansion on days 7 and 28. Cardiac ultrasound and survival analyses were performed to evaluate the cardiac function and survival rate. Adverse remodeling was determined by Wheat Germ Agglutinin (WGA) and Masson trichrome staining.
The FDG-PET (inflammation) imaging revealed that MCC950 treatment led to lower F-FDG inflammatory uptakes, at the infarct region, on days 3 and 5 when compared to the MI group. The decreased M1 macrophages and neutrophils infiltration and the remission of the NLRP3/IL-1β pathway, confirmed the FDG-PET (inflammation) imaging results. The FDG-PET (viability) imaging revealed that MCC950 significantly decreased the expansion of the viability defect, demonstrating its myocardial preservation effects. The acute FDG-PET (inflammation) signal positively correlated with the late viability defect and with the reduction in the left ventricular ejection fraction (LVEF). Additionally, the alleviated adverse remodeling and the improved survival rate further support the anti-inflammatory efficiency of MCC950 in AMI.
Using F-FDG PET imaging, we noninvasively demonstrated the therapeutic effects of MCC950 in AMI and showed that F-FDG PET imaging holds promising application potentials in MCC950's clinical translation.
MCC950 是一种新型的 NLRP3 炎性体抑制剂，在急性心肌梗死（AMI）中具有强大的抗炎作用。然而，缺乏非侵入性监测方法限制了其潜在的临床转化。因此，我们试图研究 F-FDG PET 成像是否可以监测 AMI 小鼠模型中 MCC950 的治疗效果。
使用 C57BL/6 小鼠建立 AMI 模型。MCC950 或无菌生理盐水在手术后 1 小时内腹腔内给药，然后连续 7 天每天给药。F-FDG PET（炎症）成像用于监测第 3 天和第 5 天的炎症变化。免疫组织化学和 Western blot 用于检测炎症标志物，并证实 PET 成像结果。F-FDG PET（存活）成像用于定量第 7 天和第 28 天的存活缺陷扩展。心脏超声和生存分析用于评估心功能和生存率。小麦胚凝集素（WGA）和 Masson 三色染色用于确定不良重塑。
FDG-PET（炎症）成像显示，与 MI 组相比，MCC950 治疗导致梗死区域的 F-FDG 炎症摄取在第 3 天和第 5 天降低。减少的 M1 巨噬细胞和中性粒细胞浸润以及 NLRP3/IL-1β 途径的缓解，证实了 FDG-PET（炎症）成像结果。FDG-PET（存活）成像显示，MCC950 显著减少了存活缺陷的扩展，显示出其心肌保护作用。急性 FDG-PET（炎症）信号与晚期存活缺陷以及左心室射血分数（LVEF）的降低呈正相关。此外，减轻的不良重塑和提高的生存率进一步支持了 MCC950 在 AMI 中的抗炎效率。
使用 F-FDG PET 成像，我们非侵入性地证明了 MCC950 在 AMI 中的治疗效果，并表明 F-FDG PET 成像在 MCC950 的临床转化中具有有前途的应用潜力。
