Molecular PET-MRI of Factor XIII activity for the detection of intravascular thrombosis and differentiation of its role in myocardial wound healing

因子 XIII 活性的分子 PET-MRI 用于检测血管内血栓形成及其在心肌伤口愈合中的作用

• 批准号: 209784382
• 负责人: Privatdozent Dr. Timo Sebastian Heidt
• 金额: --
• 依托单位: Center for Systems Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/209784382?language=en
• 关键词: Molecular; PET; MRI; Factor; XIII

Despite recent advances in heart failure research, more than 300 000 people die each year from ischemic cardiomyopathy. On the quest for new therapeutic strategies, in vivo molecular imaging allows for new approaches towards identifying the cellular and molecular mechanisms of its pathophysiology. Hereby, Factor XIII was identified as a key enzyme in post ischemic wound healing. The origin of factor XIII involved in this process is still unknown, either plasmatic from intravascular coagulation or cellular as it is found in monocytes and macrophages. First, this study aims on constructing a 18F-labelled probe for PET detection of factor XIII activity using a mouse carotid artery thrombosis model. This is also of clinical interest, since the detection of factor XIII activity in a carotid thrombosis model would be a novel tool for direct and sensitive imaging of acute arterial thrombosis.In a next step the probe is applied in a mouse model of myocardial infarction using PET-MRI. Factor XIII activity related uptake will be correlated with macrophage infiltration of the infarcted tissue assessed by nanoparticle MRI, before and after macrophage depletion with clodronate liposomes. The correlation of factor XIII activity with macrophage infiltration in live myocardial tissue could allow for a differentiation between the effects of plasmatic and cellular factor XIII in myocardial wound healing.

尽管心力衰竭研究最近取得了进展，但每年仍有超过30万人死于缺血性心肌病。在寻求新的治疗策略方面，体内分子成像为确定其病理生理学的细胞和分子机制提供了新的方法。因此，因子XIII被确定为缺血后创面愈合的关键酶。参与这一过程的XIII因子的来源尚不清楚，无论是来自血管内凝血的血浆还是单核细胞和巨噬细胞中的细胞。首先，本研究旨在利用小鼠颈动脉血栓模型构建18F标记的探针，用于PET检测凝血因子XIII的活性。这也是临床上感兴趣的，因为在颈动脉血栓模型中检测XIII因子的活性将是一种直接和灵敏的急性动脉血栓成像的新工具。在下一步，该探针将应用于使用PET-MRI的小鼠心肌梗死模型。因子XIII活性相关的摄取将与巨噬细胞在用氯屈膦酸盐脂质体耗竭前后的巨噬细胞在梗死组织中的渗透相关。活体心肌组织中凝血因子XIII活性与巨噬细胞浸润的相关性可以区分血浆和细胞因子XIII在心肌创面愈合中的作用。