HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis

Pellico, Juan; Fernandez-Barahona, Irene; Ruiz-Cabello, Jesus; Gutierrez, Lucia; Munoz-Hernando, Maria; Sanchez-Guisado, Maria J.; Aiestaran-Zelaia, Irati; Martinez-Parra, Lydia; Rodriguez, Ignacio; Bentzon, Jacob; Herranz, Fernando

Publicación: ACS APPLIED MATERIALS & INTERFACES
2021
VL / 13 - BP / 45279 - EP / 45290
abstract
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.

Access level

Green submitted, Green published, Hybrid

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