Multivalent Hosts for Hyperpolarized Xenon Enabling in vivo MRI Visualization of Tumor Cell SurfaceGlycans

新型非侵入性诊断成像技术在个性化医疗的概念中备受追捧，以促进更好的治疗监测和改进的药物开发。传统的磁共振成像（MRI）可以成为关键技术之一，但限于检测相当丰富的分子。由于99.999%的分子在这项技术中保持“沉默”，MRI具有很大的未使用潜力。最近开发的特殊技术在MRI扫描之前通过称为自旋超极化的过程在有限的时间内释放这种潜力。在分子示踪剂中某些核被超极化的典型方法不能进入靶组织，其中递送和特异性摄取超过超极化的寿命。通过功能化的分子单元寻址靶标，并且随后仅将这些报告分子与超极化核原位结合，显著地扩展了应用范围。氙生物传感器正是利用了这一想法，可以以108倍的采集时间以出色的灵敏度进行检测。然而，在活体组织中的应用仍然缺乏。在这个跨学科的项目中，我们将开发新的纳米载体，可以接受大量的超极化核。通过将这种传感器平台设计与超极化氙生产和溶解惰性气体相关检测技术的互补进展相结合，我们的目标是可视化具有挑战性的生物标志物，如肿瘤细胞表面聚糖。

Novel non-invasive diagnostic imaging techniques are highly sought after within the concept of personalized medicine for fostering better therapy monitoring and improved drug development. Conventional magnetic resonance imaging (MRI) can become one of the key technologies but is, however, limited to the detection of rather abundant molecules. With 99.999% of the molecules remaining "silent" in this technique, MRI has a large unused potential. Recently developed special techniques unleash this potential for a limited amount of time through a process called spin hyperpolarization prior to the MRI scan. The typical approach with certain nuclei being hyperpolarized in a molecular tracer fails to access target tissues where delivery and specific uptake exceeds the lifetime of the hyperpolarization. Addressing the target through functionalized molecular units and only combining these reporters subsequently with the hyperpolarized nuclei in situ significantly expands the range of applications. Xenon biosensors exactly capitalize on this idea and can be detected with outstanding sensitivity with 108-fold reduced acquisition times. However, applications in living tissue are still lacking. In this interdisciplinary project, we will develop novel nanocarriers that are receptive for a large number of hyperpolarized nuclei. By combining this sensor platform design with complementary advances in production of hyperpolarized xenon and related detection techniques for the dissolved noble gas, we aim for the visualization of challenging biomarkers such as tumor cell-surface glycans.