The combination of radioisotopes and nanomaterials permits the design of novel nano-radiomaterials (NRM) for multimodal imaging. The success of nanoplatform-based imaging probes is sometimes hampered by the small percentage of nanoparticles reaching the area of interest. To improve this, we have combinedly used NRM and bioorthogonal chemistry. Using the tetrazine ligation and 68Ga core-doped iron oxide nano-radiomaterials (68Ga-NRM) we have been able to detect atherosclerosis and thrombi formation, non-invasively, early in disease development. For atherosclerosis, a trans-cyclooctene (TCO) moiety was covalently attached to the antibody E-06, an IgM targeting oxidized phospholipids, while for thrombi detection we used anti-CD41 antibody, an IgG targeting platelets. Then, we synthesized the 68Ga-NRM: citrate-coated iron oxide nanoparticles core-doped with 68Ga. The 68Ga-NRM synthesis was carried out through microwave-assisted synthesis taking only 15 minutes to obtain the pure, ready-to-use sample. We next incorporated the tetrazine (TZ) moiety to the 68Ga-NRT surface through amide formation between benzylamino-tetrazine and the carboxylic acid groups in citrate. We characterized the 68Ga-NRT and, then, we performed in vivo PET/CT and ex vivo MR imaging experiments in mice models for atherosclerosis and thrombi formation, allowing for an early unambiguous detection of both diseases. Our results demonstrate the ability of this approach to detect and characterize atherosclerotic plaque and thrombi in murine models.

Bioorthogonal nano-radiomaterials for the non-invasive diagnosis of cardiovascular diseases

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.