An Ultralong-Circulating Tantalum-Based Computed Tomography Contrast Agent for Vascular Imaging in Large Animals

Abstract

Computed tomography angiography (CTA) is a critical tool for the diagnosis and prognostic evaluation of vascular diseases in clinical practice, but current CT contrast agents fall short of meeting the demands for real-time, long-term, and high-resolution imaging. This study presents an ultra-long-term CTA method enabled by PEGylated ultrasmall tantalum oxide nanoparticles (Ta₂O₅-PEG NPs) for accurate imaging evaluation of cardiovascular diseases based on the blood clearance mechanism of NPs. This contrast agent featured exceptional water solubility (800 mg mL^-1), strong X-ray attenuation, good biocompatibility, and large-scale production ability. With a compact hydrodynamic diameter (∼10 nm) and nearly neutral surface charge, Ta₂O₅-PEG NPs exhibited prolonged blood circulation (half-lives of 19.84 h in rats and 18.23 h in rabbits) and an extended imaging window of up to 10 h post-injection. Comparative studies in rat, rabbit, and preclinical porcine models demonstrated that Ta₂O₅-PEG NPs enabled high-resolution, whole-body vascular visualization, and supported accurate diagnosis and postoperative evaluation of vascular stenosis and thrombosis from single administration. The proposed ultra-long-term CTA strategy, leveraging non-iodinated high atomic number elements, offers a precise imaging approach with clinical translation potential for the pre- and post-treatment evaluation of vascular diseases.

Keywords: CT imaging; cardiovascular diseases; contrast agent; long circulation; tantalum oxide.