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

本方案旨在利用基于19F-纳米粒子的19F-磁共振断层扫描(19F-MRI)在动物模型上无创地成像心肌梗死后的亚急性愈合阶段。心肌梗死后的炎症是心肌愈合和随后的心肌重塑的主要决定因素。在这一愈合过程中，巨噬细胞扮演着重要的角色，同时它们调节炎症过程并组织结缔组织的组装。愈合过程和涉及的炎症细胞可能是治疗干预的靶点。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MR技术，已经在9.4特斯拉高场MRI环境下的实验性炎症小鼠模型中得到验证。与其他磁共振造影剂相比，这种方法的主要优点是它能够直接定量，而且由于体内没有任何氟背景，因此具有高度的特异性。此外，单核/巨噬细胞由于其吞噬能力而被选择性地作为靶标。最近，我们可以证明使用临床扫描仪(3特斯拉)的19F-MRI在猪移植心脏心肌梗死的临床前模型中的可行性。因此，本建议有以下具体目的：1.验证在体MRI成像方法，用19F-MRI2以多参数的方式表征猪心肌梗死后的亚急性愈合阶段。~(19)F-纳米颗粒在猪和人单核细胞中的摄取特征，以及在网状内皮系统(RES)器官和猪心脏中的摄取；3.用MRI显示再灌流和非再灌流心肌梗死后亚急性愈合期的炎性细胞，并与组织学验证。

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.