Imaging human cardiovascular macrophages using 64Cu-Macrin positron emission tomography

Macrophages are protagonists and therapeutic targets in numerous cardiovascular diseases, though no therapies specifically targeting macrophages are licensed for patient use.

A major barrier to clinical development of novel macrophage-targeting therapeutics is the absence of imaging technologies which could non-invasively detect and quantitatively assess macrophages in the human cardiovascular system.

We propose an initial human translational cardiovascular study to test a novel polyglucose nanoparticle positron emission tomography (PET) probe which has been specifically designed to detect macrophages and has outstanding imaging performance in preclinical studies: 64Cu-Macrin.

To define the ability of 64Cu-Macrin to detect macrophages within human myocardium following acute myocardial infarction (MI), we will perform cardiovascular PET using 64Cu-Macrin in patients with and without acute MI.

In addition, we will perform 18F-fluorodeoxyglucose (FDG) PET as a benchmark against which to test the imaging performance of 64Cu-Macrin, and cardiovascular magnetic resonance (CMR) to characterise the myocardium and investigate links between macrophage signal and left ventricular remodelling.

If successful, the validation of 64Cu-Macrin as a non-invasive probe for human cardiac macrophages would provide a step-change in our ability to study macrophage biology in human cardiovascular disease and could accelerate the development of novel macrophage-targeting therapies.