Myocardial platelet imaging with [¹8F]GP1 positron emission tomography identifies a platelet-dominant microvascular injury phenotype after ST-segment elevation myocardial infarction

Background Following epicardial reperfusion after ST-segment elevation myocardial infarction, no-reflow phenomenon from myocardial microvascular obstruction is a major clinical problem. The underlying mechanisms are unclear but have been proposed to include vasoconstriction and tissue oedema. Platelet activation may contribute through distal embolisation and plugging of the microcirculation, although direct in vivo evidence linking platelet activation to myocardial microvascular obstruction is lacking. The radiotracer, [¹8F]GP1, binds activated glycoprotein IIb/IIIa receptors expressed on activated platelets, enabling targeted non-invasive imaging of platelet activation and thrombosis. Methods In a single centre observational study, 100 patients with acute anterior ST-segment elevation myocardial infarction underwent hybrid [¹8F]GP1 positron emission tomography (PET) and cardiac magnetic resonance (CMR) at a median of 13 days after infarction. Myocardial uptake was assessed qualitatively and quantified using target-to-background ratio (TBRmax) and percentage myocardial uptake. Associations with infarct size and microvascular obstruction on CMR were examined using regression analyses. Patients with myocardial [¹8F]GP1 uptake underwent repeat imaging at 3–6 months. Results Myocardial [¹8F]GP1 uptake occurred in 44% of participants and co-localised with infarcted myocardial territories (Figure 1A, 1C and 2B). Microvascular obstruction on CMR was fully concordant with myocardial [¹8F]GP1 uptake. Myocardial PET [¹8F]GP1 burden exceeded CMR-defined burden by a mean of 18%. Microvascular obstruction burden correlated strongly with myocardial [¹8F]GP1 uptake intensity (Spearman ρ = 0.78; p<0.001) and burden (Spearman ρ = 0.84; p<0.001) independent of infarct size. Angiographic no-reflow was the strongest independent association with microvascular obstruction (adjusted odds ratio 16.15; p<0.001) (Figure 2A). In patients with follow up imaging, 7/32 (22%) had persistent myocardial [¹8F]GP1 uptake at 6 months which was associated with lower left ventricular ejection fraction. (Figure 1B). Conclusions We provide the first direct in vivo evidence that microvascular obstruction following ST-segment elevation myocardial infarction is universally associated with microcirculatory platelet activation, suggesting the predominant mechanism is microcirculatory thrombosis. Importantly, myocardial [¹8F]GP1uptake extended beyond regions of CMR defined microvascular obstruction and enables serial quantification of uptake intensity and burden over time. Persistent [¹8F]GP1 uptake was associated with lower left ventricular ejection fraction at follow up, implicating the role of sustained platelet activation in ongoing functional impairment. This approach may enable mechanistic stratification and serve as a pharmacodynamic imaging biomarker for therapies targeting platelet activation, microvascular thrombosis, and thrombo-inflammatory pathways.