Xenon‐MRT an lebenden Zellen mit Hyper‐CEST‐Biosensoren für metabolisch markierte Glykane an der Zelloberfläche

Abstract

Das Targeting von metabolisch markierten Glykanen mit herkçmmlichen MRT-Kontrastmitteln erschien bislang als nicht realisierbar. Hier erweitern wir die Anwendungen von Xenon-Hyper-CEST-Biosensoren in Zellen und präsentieren damit die erste erfolgreiche molekulare Bildgebung dieser Glykane mittels MRT. Hyper-CEST-Biosensoren sind eine neue Klasse von MRT-Kontrastmitteln mit sehr hoher Empfindlichkeit. Darauf basierend wurde ein multimodaler Biosensor für sowohl Fluoreszenz-als auch Xenon-MRT-Detektion entwickelt, der selektiv mit metabolisch markierten Sialinsäuren durch bioorthogonale Chemie verknüpft wurde. Die Verwendung eines kürzlich entwickelten Bioreaktors zur Untersuchung lebender Zellen ermçglicht somit den Nachweis von Zelloberflächenglykanen mittels Xenon-MRT bei nanomolaren Konzentrationen.

High Exchange Rate Complexes of 129Xe with Water‐Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI

“…They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of watersoluble pillar [5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation.…”

“…Protein structures for trapping Xe have also been investigated [14][15][16] as a genetically expressible host version, but their complexity makes it rather tedious to further tune the chemical shift and exchange properties through chemical engineering. Thus, this currently active field of method development for biomedical imaging applications is seeking additional concepts for Xe hosts based on simple building blocks to extend the range of sensor applications.Pillar [5]arenes are another class of macrocyclic hosts having a relatively rigid cylindrical structure capable of encapsulating both charged and neutral guests. First reported by Ogoshi et al [17] , they have been investigated as a platform in host-guest chemistry.…”

“…Pillar [5]arenes are another class of macrocyclic hosts having a relatively rigid cylindrical structure capable of encapsulating both charged and neutral guests. First reported by Ogoshi et al [17] , they have been investigated as a platform in host-guest chemistry.…”

NMR Hyperpolarization Techniques of Gases

“…[151] An indirect binding approach was pursued through in situ click chemistry with metabolically labeled cell surface glycans. [152] Conformational changes of the sensor induced by changes in pH represent an approach for stimulus-induced binding. [153] As part of these studies, cell uptake and toxicity evaluations set the bar for target concentrations of functionalized hosts.…”

“…However, they are not an absolute requirement since the hydrophobic character of CrA can mediate membrane-association and therefore enables certain types of cellular labeling. [155] Sensors with highly specific binding motifs (e.g., antibodies [147,150] or bioorthogonal reaction partners [152] ) only require sample-averaged concentrations of 10 -8 M for MRI.…”