Articular cartilage is the smooth, hydrated tissue that lines the ends of long bones in load bearing joints. The heavily sulfated and carboxylated polysaccharides comprising the glycosaminoglycans (GAGs) represent 5-10 % by wt of articular cartilage, and are key components in conferring cartilage with its resistance to compressive loads. The remaining mass of cartilage is composed mostly of collagen (10-20%) and water (68-85%). It is widely recognized that the loss of GAGs from the articular cartilage is a hallmark of osteoarthritis, a degenerative joint disease in which wear or trauma results in damage to the articular cartilage surface. Consequently, imaging techniques capable of assessing local variations in GAG content are of significant interest for the study of cartilage biology and for the diagnosis of cartilage diseases. Magnetic resonance (MR) and computed tomography (CT) imaging modalities have been used to image cartilage and both imaging modalities use anionic contrast agents which must diffuse into the target tissue. We hypothesized that cationic contrast agents would be electrostatically attracted to anionic GAGs, and would consequently result in a more sensitive technique for imaging cartilage.
In order to investigate the effects of contrast agent charge on CT imaging, we synthesized three new iodinated contrast agents – one having a single positive charge and three iodine atoms (CA1+), a second having two positive charges and three iodine atoms (CA2+), and a third having four positive charges and six iodine atoms (CA4+). These molecules were compared to two commercial formulations of anionic contrast agents, Cysto Conray II® (1; iothalamate) and Hexabrix® (2; ioxaglate). We next imaged the distal end of an ex vivo rabbit femur after immersion in one contrast agent using micro computed tomography (microCT40). Images obtained from the rabbit femur studies show that the cationic contrast agents afforded higher x-ray attenuation values and more specific imaging for the cartilage tissue as compared to the anionic contrast agents (see Figure ). The cationic contrast agents had 1.6 (CA1+), 2.4 (CA2+), and 2.9 (CA4+) times higher mean attenuation values for cartilage than their anionic counterparts, indicating that increasing cationic charge yielded higher affinities for the anionic fixed charge density of GAGs.