Keilian MacCulloch , Austin Browning , David O. Guarin Bedoya , Stephen J. McBride , Mustapha B. Abdulmojeed , Carlos Dedesma , Boyd M. Goodson , Matthew S. Rosen , Eduard Y. Chekmenev , Yi-Fen Yen , Patrick TomHon , Thomas Theis
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引用次数: 3
Abstract
Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1–13C]pyruvate. Biocompatible formulations of hyperpolarized [1–13C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.
基于对氢可逆交换的超极化化学,也称为可逆交换信号放大(SABRE),是获得高水平核自旋超极化的一种特别简单的方法,可以将核磁共振和核磁共振信号增强许多数量级。自SABRE问世以来,由于其相对简单的实验和广泛的分子适用性,在科学界受到了极大的关注,然而,通过SABRE进行超极化分子探针的体内检测仍然难以捉摸。在这里,我们描述了首次在体内检测sabre超偏振造影剂的演示,特别是使用超极化[1-13C]丙酮酸。在甲醇-水和乙醇-水混合物中制备具有生物相容性的超极化[1-13C]丙酮酸制剂,然后用生理盐水稀释和催化剂过滤,并注射到健康的Sprague Dawley和Wistar大鼠体内。用二氧化硅过滤器进行了有效的超极化-催化剂去除,而超极化损失不大。在体内检测了丙酮酸转化为乳酸、丙氨酸和碳酸氢盐的代谢。水合物丙酮酸也被观察到是一个次要的副产物。在4.7 T时,通过时间分辨光谱和化学位移分辨MRI对肝脏和肾脏进行测量。此外,使用无低温1.5 T MRI系统获得了全身代谢测量,说明了将低成本MRI系统与简单,低成本的超极化化学相结合以开发安全且可扩展的分子成像的有效性。