PM.20.060 – Personalised management of atherosclerosis using a novel imaging technique

Route: Personalised medicine: the individual at the centre

Cluster question: 088 How can we predict, prevent, and treat cardiovascular diseases (atherosclerosis, heart failure, heart arrhythmia, and thrombosis) in individuals at an early stage?

Inflammation is a key factor in a wide range of cardiovascular diseases, and acute myocardial infarction is one of the leading causes of death in the western world. FDG-PET imaging is now considered as gold standard in nuclear imaging of myocarditis and pericarditis, and experimental in diagnosis and monitoring of (coronary) atherosclerosis. However, the non-specific cardiac uptake by the myocardium is an important limitation, decreasing diagnostic accuracy. We have developed a new and better approach using a novel and unique nuclear tracer which is very specific to inflammation, and overcomes this and other limitations of FDG-PET in cardiac imaging. We propose a novel imaging strategy for inflammation, by specifically targeting Leukocyte Function-associated Antigen-1 (LFA-1). This is an integrin cell-surface receptor expressed on leukocytes and binds to intracellular adhesion molecule-1 (ICAM-1) on antigen presenting cells. LFA-1 is expressed by several types of inflammatory cells, including macrophages, but also by T-cells, B-cells, and neutrophils. Previous studies show LFA-1 to be a target for inflammation mitigating therapy in myocardial infarction and atherosclerosis. In our pre-clinical studies, we were indeed able to clearly image inflammation in atherosclerosis. Recent studies show clear patient benefits of anti-inflammatory therapy, such as colchicine, after myocardial infarction. However, currently we are unable to identify the patients that benefit most. Imaging of LFA-1 expression in patients may therefore be highly relevant, providing a better understand of the inflammatory response in coronary artery disease. It may identify patients for optimal anti-inflammatory treatment strategies and monitor responses to this therapy. This may also result in a screening tool, preventing serious events such as myocardial infarction by timely initiation of lifestyle changes and medical treatment. We therefore propose a first-in-human non-invasive imaging study of coronary inflammation using this novel tracer and evaluate the effect of anti-inflammatory treatment in individual patients.

Keywords

atherosclerosis, imaging, inflammation, myocardial infarction, treatment

Submitter

Organisation Erasmus MC (EMC)
Name Dr. B.J. (Boudewijn) Krenning
E-mail b.krenning@erasmusmc.nl