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, [F-18]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonatefunctionalized Ga-68 core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (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/(T-1)MRI during the vulnerable stages of the plaque progression.

Automated summary

Vascular microcalcifications are associated with atherosclerosis plaque instability and increased mortality, with imaging probes such as [F-18]FNa playing a key role in their in vivo identification. The development of HAP-multitag shows promise in early characterization of atherosclerosis, with potential for identifying lesion progression and calcification stages using PET/(T-1)MRI imaging.