Autor: |
Pellico J; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; School of Biomedical Engineering & Imaging Sciences, King's College London, St. Thomas' Hospital, SE1 7EH London, U.K., Fernández-Barahona I; Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.; NanoMedMol Group, Instituto de Química Medica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), 28006 Madrid, Spain., Ruiz-Cabello J; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.; Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia San Sebastián, Spain.; IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain., Gutiérrez L; Departamento de Química Analítica, Instituto de Nanociencia y Materiales de Aragón, Universidad de Zaragoza-CSIC y CIBER-BBN, 50018 Zaragoza, Spain., Muñoz-Hernando M; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.; NanoMedMol Group, Instituto de Química Medica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), 28006 Madrid, Spain., Sánchez-Guisado MJ; Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia San Sebastián, Spain., Aiestaran-Zelaia I; Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia San Sebastián, Spain., Martínez-Parra L; Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia San Sebastián, Spain., Rodríguez I; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain., Bentzon J; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain., Herranz F; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; NanoMedMol Group, Instituto de Química Medica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), 28006 Madrid, Spain. |
Abstrakt: |
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, [ 18 F]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 bisphosphonate-functionalized 68 Ga 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. |