Computed Tomography of Cartilage: An Exploration of Novel Cationic Bismuth Contrast Agent

Accurate diagnosis of minor cartilage injuries with delayed contrast-enhanced computed tomography (CECT) is challenging as poor diffusion and toxicity issues limit the usage of common CT contrast agents. Hence, the design of safe contrast agents with physiochemical properties suitable for fast, deep cartilage imaging is imminent. Herein, a novel cationic bismuth contrast agent (Bi-DOTAPXD) based on dodecane tetraacetic acid (DOTA) was synthesized and examined for CECT of cartilage. The complex was designed to improve diagnosis by utilising a net-positive charge for enhanced permeability through cartilage, inherent low-toxicity and high X-ray attenuation of bismuth. Osteochondral plugs (n = 12), excised from visually intact porcine articular cartilage were immersed in Bi-DOTAPXD (8 mg/mL) and Gd-DOTAPXD (10 mg/mL) contrast agents and scanned with a high-resolution microcomputed tomography scanner at multiple time-points. The mean Bi-DOTAPXD and Gd-DOTAPXD partitions at 45-min time-point were 85.7 ± 35.1 and 69.8 ± 30.2%, and the partitions correlated with the histopathological analysis of cartilage proteoglycan (PG) content (r) at 0.657 and 0.632, respectively. The time diffusion constants (τ) for Bi-DOTAPXD and Gd-DOTA were 121 and 159 min, respectively. Diffusion Bi-DOTAPXD and Gd-DOTAPXD reflected inter-sample variation in cartilage PG content. Cationic Bi-DOTAPXD may have the potential as a CT agent for the diagnosis of cartilage.