Abstract
Introduction: Coronary artery disease (CAD) causing symptomatic ischemia is often missed in patients that present with angina pectoris but without ECG changes or rise in troponin. A sensitive diagnostic test that could diagnose an ischemic event, before cardiac damage is causing troponin release, would change the clinical path of emergency patients with angina and reduce the number of CAD patients to remain undiagnosed and thus have an increased risk of myocardial infarction. Methods: We developed a sensitive, non-invasive imaging approach using PET imaging of activated platelets for the detection of minimal cardiac ischemia and inflammation. Different extents of ischemia were induced in mice by temporary LAD ligation for 10, 20 or 60 min. Activated platelets were imaged in a PET/CT scanner with 64 Cu bound to the chelator MeCOSar that was conjugated to a single-chain antibody directed against activated GPIIb/IIIa. Results: A time course of platelet adhesion within the infarcted myocardium indicates an early inflammatory response of activated platelets to the ischemic insult peaking 2h post reperfusion. Sensitive biomarkers such as troponin I and heart-type fatty acid-binding protein (H-FABP) could not detect smaller degrees of cardiac ischemia (10 and 20 min of ischemia). In contrast, PET-based imaging of activated platelets detects even minor degree of ischemia. The significant adhesion of platelets in the ischemic heart even after minor degrees of ischemia was confirmed by flow cytometry and histology. Conclusions: Cardiac ischemia is associated with a significant adhesion of activated platelets within the ischemic heart. Even minimal extents of cardiac ischemia not associated with troponin rises are detectable by platelet-based PET imaging. This novel, highly sensitive non-invasive detection of minimal degrees of cardiac ischemia has the potential to detect otherwise undetected CAD. Figure: PET/CT imaging of activated platelets within ischemic hearts.
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