Simple Host–Guest Assembly for High-Resolution Magnetic Resonance Imaging of Microvasculature

Abstract

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 (r 1 = 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.

Utility of 1.5 Tesla MRI Scanner in the Management of Small Sample Sizes Driven from 3D Breast Cell Culture

“…It has been postulated that slower average motion of water in cells to long- [ 66 ] and short-range interactions between water molecules and macromolecular surfaces. MR has been used by a number of investigators to examine the behavior of water molecules in whole organisms [ 67 ], normal and cancerous tissues of many kinds [ 68 ], in cultured cells [ 69 ] during the cell cycle [ 70 ], and in solutions of macromolecules [ 71 ]. In all cases, the relaxation times were reduced by 3 to 100 times their value in pure liquid water.…”

Azo Reductase Activated Magnetic Resonance Tuning Probe with “Switch-On” Property for Specific and Sensitive Tumor Imaging in Vivo

“…Hypoxia is a common feature of most solid tumors, , and it can cause an increase in reductive stress, which leads to high levels of reductase expression in tumor sites, such as quinone reductase (QR), nitro-reductase (NTR), and azo reductase (AzoR) . Among them, AzoR is an important family of reductases that can gradually reduce the azo bond to anilines and has been successfully used in the design of many small-molecule probes. − As an ideal substrate for AzoR, azobenzene (Azo), and cyclodextrin could form stable host–guest complexes which have been extensively employed for in vivo imaging and drug delivery study. − Herein, we presented a kind of AzoR-activated MRET imaging probe with a “switch-on” property for specific and sensitive tumor imaging in vivo , especially for imaging tumors with smaller sizes. More specifically, a paramagnetic compound of Gd-labeled DNA 1 (DNA 1 -Gd) and superparamagnetic nanoparticles of cyclodextrin-coated magnetic nanoparticles (MNP-CD) were employed as enhancer and quencher, respectively, and the azo-modified aptamer (AS1411) DNA 2 served as a linker between the enhancer and quencher to construct the MRET probe MNP@DNA (1–2) -Gd based on host–guest interaction between Azo and cyclodextrin. − As shown in Figure , in normal tissues the nanoscale distance between DNA 1 -Gd and MNP-CD was sufficiently close, allowing the probe to remain in a constant “OFF state”.…”