In vivo imaging of inflammation with 19F-MRI in the subacute healing phase after myocardial infarction

本研究旨在利用基于19f纳米颗粒的19f磁共振断层扫描（19F-MRI）在转译动物模型中对心肌梗死后亚急性愈合期进行无创成像。心肌梗死后的炎症是心肌愈合和随后心肌重构的主要决定因素。在这一愈合过程中，巨噬细胞在调节炎症过程和组织结缔组织组装方面发挥着重要作用。愈合过程和涉及的炎症细胞是治疗干预的可能目标。因此，对炎症尤其是巨噬细胞在心肌梗死后心肌愈合过程中的关键作用进行成像和表征是非常必要的。19F-MRI是一种核磁共振技术，已经在实验性炎症小鼠模型中得到验证，高场MRI为9.4特斯拉。与其他核磁共振造影剂相比，该方法的主要优势在于其可直接量化的能力以及由于体内没有任何氟背景而具有的高特异性。此外，单核细胞/巨噬细胞因其吞噬能力而被选择性靶向。最近，我们可以在移植猪心脏的临床前模型中使用临床扫描仪（3特斯拉）证明19F-MRI的可行性。因此，本提案有以下具体目的：体内mri成像方法的验证，用19F-MRI2以多参数方式表征猪心肌梗死后亚急性愈合期。猪和人单核细胞对19f纳米颗粒的摄取特性，以及网状内皮系统（RES）器官和猪心脏的摄取特性。再灌注和非再灌注心肌梗死后亚急性愈合期炎症细胞的MRI可视化和组织学验证。

The present proposal aims to non-invasively image the subacute healing phase after myocardial infarction with 19F-magnet resonance tomography (19F-MRI) based on 19F-nanoparticles in a translational animal model. Inflammation after myocardial infarction is a major determinant of myocardial healing and subsequent myocardial remodeling. In this healing process, macrophages play an important role, while they modulate inflammatory processes and organize the assembly of connective tissue. The healing process and the involved inflammatory cells are a possible target of therapeutic intervention. Thus, it is highly desirable to image and to characterize inflammation and especially macrophages as key players in the myocardial healing process after myocardial infarction.19F-MRI is a MR-technique which has already been validated in experimental inflammatory mice models in the setting of high-field MRI at 9.4 Tesla. The major advantage of this approach in comparison to other MR-contrast agents is its capability of being directly quantifiable and its high specificity due to the lack of any fluorine background in the body. Besides that, monocytes/macrophages are selectively targeted due to their phagocytic capacity. Recently, we could demonstrate the feasibility of 19F-MRI using a clinical scanner (3 Tesla) in a preclinical model of myocardial infarction in explanted pig hearts.Therefore, the present proposal has the following specific aims:1. Validation of an in vivo MRI-imaging approach, characterizing the subacute healing phase after myocardial infarction in pigs in a multiparametric manner with 19F-MRI2. Characterization of 19F-Nanoparticle uptake in monocytes of pig and man, as well as the uptake in organs of the reticulo endothelial system (RES) and in the pig heart and 3. Visualization of inflammatory cells in the subacute healing phase after reperfused and non-reperfused myocardial infarctions with MRI and validation with histology.