HAP-multitag, a PET and positive MRI contrast nanotracer for the longitudinal characterization of vascular calcifications in atherosclerosis

Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them [18F]FNa is the gold standard, showing a large uptake in the whole skeleton. Here, we push the field towards the combined anatomical and functional early characterization of atherosclerosis. For that, we have developed HAP-multitag, a bisphosphonate-functionalized 68Ga magnetic nanoparticle showing high affinity towards most common calcium salts present in microcalcifications, particularly hydroxyapatite. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by PET and positive contrast MRI. In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression.