Magnetic resonance angiography (MRA) is an important imaging technique that can be used to identify and characterize various types of vascular diseases. However, currently used molecular contrast agents are unsuitable for MRA due to the short intravascular retention time, the whole-body distribution, and the relatively low contrast effect. In this study, we developed a vascular analysis contrast agent (i.e., VasCA) for MRA, which is a simple and biocompatible 1:1 host-guest assembly of PEGylated β-cyclodextrin and gadolinium chelate with renal clearable size and high relaxivity (r1 = 9.27 mM-1 s-1). Its biocompatibility was confirmed by in vivo animal studies as well as in vitro 3D cell culture. In a tumor-bearing rat model, VasCA circulated in the blood vessels much longer (4.3-fold increase) than gadoterate meglumine (Dotarem) and was mainly excreted by the renal system after intravenous injection. This feature of VasCA allows characterization of tumor microvasculature (e.g., feeding and draining vessels) as well as visualization of small vessels in the brain and body organs. Furthermore, after treatment with an angiogenesis inhibitor (i.e., sorafenib), VasCA revealed the vessel normalization process and allowed the assessment of viable and necrotic tumor regions. Our study provides a useful tool for diverse MRA applications, including tumor characterization, early-stage evaluation of drug efficacy, and treatment planning, as well as diagnosis of cardiovascular diseases.
Keywords: blood-pool contrast agents; gadolinium chelate; magnetic resonance imaging; microvasculature; renal clearance; β-cyclodextrin.