Targeted PET Imaging of Atherosclerosis via Low-Density Lipoprotein Click Chemistry with Nanoparticles
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Low-density lipoprotein (LDL) plays a central role in the development of atherosclerosis, making its detection critical for cardiovascular disease management. Radionuclide imaging of LDL offers distinct advantages over other modalities but remains limited by poor specificity and the need for long-lived isotopes. We present a click chemistry-based PET imaging strategy using gallium-68 ( 68 Ga), a short-lived radionuclide, for the specific detection of LDL accumulation in atherosclerotic plaques. The approach relies on a two-step inverse electron-demand Diels–Alder reaction between trans-cyclooctene (TCO)-modified LDL and tetrazine-functionalized iron oxide nanoparticles radiolabeled with 68 Ga. In vivo PET/CT imaging in LDL receptor-deficient (LDLr –/– ) mice showed selective uptake of the nanoparticles in atherosclerotic lesions, with minimal signal in wild-type controls. This method demonstrated high specificity and sensitivity, while reducing background signal and radiation exposure. Our results support the potential of this approach as a noninvasive and translatable platform for early diagnosis and risk assessment in cardiovascular disease.
Source: Chemical & Biomedical Imaging
DOI: 10.1021/cbmi.5c00147
Institutions: Aarhus University, Spanish National Centre for Cardiovascular Research, Consejo Superior de Investigaciones Científicas, Instituto de Química Médica, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Universitat Autònoma de Barcelona, Institut de Ciència de Materials de Barcelona
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: Aarhus Universitet, Institut for Klinisk Medicin, Aarhus Universitet, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, Ministerio de Ciencia e Innovación, Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia y Tecnología, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, European Social Fund
Awards: G121809054, G1599646647, G1622782223, G1623706041, G1728342668, G1855990336, G2085528529, G2262748287, G2282560502, G2309174360, G234454427, G2660406951, G2673512141, G2906055632, G3331922608, G3480869486, G3518538256, G3575570830, G3690828678, G3743529912, G425668148, G4366916377, G451917667, G4526231891, G4646777921, G4889780201, G5080475149, G5421974903, G5906468392, G5961725498, G5967599077, G6184484101, G6218905885, G6613839810, G6672109459, G7084143925, G751193162, G7664048306, G81639774, G8294824355, G8434830731, G8684520763, G897484643, G926782147
OpenAlex ID: W4415972018