Gadolinium-based contrast agents that have long circulation times in small animals have always been of interest in preclinical imaging. Although gadolinium-based contrast media are used clinically in MRI, these agents are composed of small molecules; by renal clearance, these molecules exit the blood pool of small animals before imaging can be completed. Long circulation times that are appropriate for microimaging – in the order of tens of minutes – can be achieved by using nanoparticles that are large enough to evade rapid renal clearance (i.e. over 10 nm in diameter). The encapsulation of nanoparticles within polymers is also required to minimize their detection by the immune system, thus delaying hepatic clearance. Hence, the objective of our work was to develop a gadolinium-based contrast agent that will circulate long enough for pre-clinical computed tomography (CT) while maintaining blood pool detectability in the image (i.e. initial gadolinium content of around 100 mg/mL). We synthesized a contrast agent in the form of polymerencapsulated gadolinium nanoparticles by following a method that our group has reported. The nanoparticles in the contrast agent were characterized to have an average diameter of 110 ± 3 nm, and contains 94 ± 7 mg/mL of gadolinium. Our in vivo results in 2 mice show blood pool contrast enhancements of 220 ± 22 HU and circulates for up to an hour after tail vein injection. Given that the contrast agent stays in the blood pool of mice for up to an hour, the contrast agent has promising utility in pre-clinical vascular research.
Advances in nanotechnology have led to the development of blood-pool contrast agents for micro-computed tomography (micro-CT). Although long-circulating nanoparticle-based agents exist for micro-CT, they are predominantly based on iodine, which has a low atomic number. Micro-CT contrast increases when using elements with higher atomic numbers (i.e. lanthanides), particularly at higher energies. The purpose of our work was to develop and evaluate a lanthanide-based blood-pool contrast agent that is suitable for in vivo micro-CT. We synthesized a contrast agent in the form of polymer-encapsulated Gd nanoparticles and evaluated its stability in vitro. The synthesized nanoparticles were shown to have an average diameter of 127 ± 6 nm, with good size dispersity. Particle size distribution -- evaluated by dynamic light scattering over the period of two days -- demonstrated no change in size of the contrast agent in water and saline. Additionally, our contrast agent was stable in a mouse serum mimic for up to 30 minutes. CT images of the synthesized contrast agent (containing 27 mg/mL of Gd) demonstrated an attenuation of over 1000 Hounsfield Units. This approach to synthesizing a Gd-based blood-pool contrast agent promises to enhance the capabilities of micro-CT imaging.