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

• DOI: 10.1021/acsami.1c13417
• Publication Date: 2021-09-16T20:32:31Z
• Authors: Juan Pellico; Irene Fernández-B...; Jesús Ruiz-Cabello; Lucía Gutiérrez; María Muñoz-Hernando; María J. Sánchez-...; Irati Aiestaran-Z...; Lydia Martínez-Parra; Ignacio Rodríguez; Jacob Bentzon; Fernando Herranz
• Keywords: Vascular calcifications; 610; Contrast Media; Gallium Radioisotopes; Multimodal Imaging; Hydroxyapatite; Aorta/pathology; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Atherosclerosis/complications; Gallium Radioisotopes/chemistry; Vascular Calcification; Magnetic Iron Oxide Nanoparticles/chemistry; Aorta; Durapatite/chemistry; Alendronate; Contrast Media/chemistry; Vascular Calcification/diagnostic imaging; hydroxyapatite; vascular calcifications; Plaque, Atherosclerotic/diagnosis; Atherosclerosis; Magnetic Resonance Imaging; Plaque, Atherosclerotic; Nanotracer; 3. Good health; PET/MRI; Durapatite; Alendronate/chemistry; Positron-Emission Tomography; nanotracer; Magnetic Iron Oxide Nanoparticles; atherosclerosis

ABSTRACTVascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for theirin vivoidentification. 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-functionalized68Ga magnetic nanoparticle showing high affinity towards most common calcium salts present in microcalcifications, particularly hydroxyapatite. We characterized this interactionin vitroandin 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.