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

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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.