High-concentration gadolinium nanoparticles for pre-clinical vascular imaging

Abstract

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.