Molecular Sensing with Host Systems for Hyperpolarized 129Xe

Abstract

Hyperpolarized noble gases have been used early on in applications for sensitivity enhanced NMR. 129Xe has been explored for various applications because it can be used beyond the gas-driven examination of void spaces. 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. Moreover, the transient nature of gas binding in such hosts allows the combination with another signal enhancement technique, namely chemical exchange saturation transfer (CEST). 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. This review summarizes developments in biosensor design and synthesis for achieving molecular sensing with NMR at unprecedented sensitivity. 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. 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.

Rapid analytical CEST spectroscopy of competitive host–guest interactions using spatial parallelization with a combined approach of variable flip angle, keyhole and averaging (CAVKA)

“…It is important to be aware of the non-linearity of the CEST response which is linked to the increasing problem of back exchange of already saturated magnetization as the depletion progresses. 6 CEST effects exceeding 25-30% of signal depletion cannot be compared any more as linear changes in the concentration. The CEST response in the CB7 sample under this condition is already 45% and thus requires the fitting analysis according to the FHC model for which CAVKA delivers reliable spectra in a short time for direct comparison between samples.…”

19F MRI Probes for Multimodal Imaging**

“…Hyperpolarization of 129 Xe is typically used to enhance the sensitivity and significantly shorten the acquisition time. In vivo applications and physical principles of this modality have been the subject of numerous reviews published in recent years [147,148] …”

“…In vivo applications and physical principles of this modality have been the subject of numerous reviews published in recent years. [147,148] Until now, only one publication has explored the 19 F- 129 Xe MRI combination with OFI as a third modality. The design of the probe relied on the PFOB-nanoemulsion system (Figure 54).…”

Hyper-CEST NMR of metal organic polyhedral cages reveals hidden diastereomers with diverse guest exchange kinetics

“…The magnetization in the bound pool is saturated by utilizing a continuous wave rf pulse applied over a time that is significantly longer than the average residence time of transiently bound spins. During this saturation period, chemical exchange causes a signal loss in bulk pool by affecting hundreds to thousands of spins per exchange site, thereby leading to accumulation of destroyed magnetization in the detection (bulk) pool 51 . ST techniques improve NMR sensitivity, retain the spectral dimension 57 , and can be “tuned” in sensitivity to different time scales of exchange processes.…”