3He, 13C, 15N, 129Xe has thus attracted much attention over the recent years. The hyperpolarization of various nuclei, incl. Fluorine ( 19F) NMR has been used in many studies as a background-free option but still does not solve the sensitivity issue with regard to minimum detectable concentrations. It can be addressed by detecting nuclei other than the abundant 1H.
The strong background signal of ubiquitous tissue water is also of concern for certain applications. They often require (a) relative high concentrations (e.g., 10–100 µM for Gd-based T 1 agents) and (b) come with limited specificity. Conventional contrast agents act as relaxivity agents on the bulk water pool.
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These techniques are key contributions to unleash the full analytical and diagnostic potential that is inherent to the NMR signal, particularly in biomedical applications. In this regard, the use of hyperpolarization techniques has opened up new possibilities in medical imaging diagnostics. This limitation is an even greater challenge for MRI and has been an active field of research for a long time. The Boltzmann distribution around room temperature yields detectable magnetization for Faraday induction only if the spin densities are relatively high. The concept is presented in the broader context of reporter design with insights from other modalities that are helpful for advancing the field of Xe biosensors.ĭespite its excellent molecular specificity, NMR has strong limitations for many applications due to its low sensitivity at physiological conditions. Aspects regarding Xe exchange kinetics and chemical engineering of various classes of hosts for an efficient build-up of the CEST effect will also be discussed as well as the cavity design of host molecules to identify a pool of bound Xe. This review summarizes developments in biosensor design and synthesis for achieving molecular sensing with NMR at unprecedented sensitivity. Different systems have been investigated for implementing various types of so-called Xe biosensors where the gas binds to a targeted host to address molecular markers or to sense biophysical parameters. Moreover, the transient nature of gas binding in such hosts allows the combination with another signal enhancement technique, namely chemical exchange saturation transfer (CEST). Its solubility in aqueous solutions and its affinity for hydrophobic binding pockets allows “functionalization” through combination with host structures that bind one or multiple gas atoms. 129Xe has been explored for various applications because it can be used beyond the gas-driven examination of void spaces. Hyperpolarized noble gases have been used early on in applications for sensitivity enhanced NMR.
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