Surface chemistry for high-contrast fluorescence kidney imaging

描述体内荧光成像，允许在一个完整的活生物体的生理过程的可视化，一直是一个不可或缺的临床前工具，疾病的病理和发展的基本理解。最近，它也被转化为临床试验，以改善手术结果和降低医疗保健成本。然而，将体内荧光成像递送到临床前肾脏研究和手术中仍然具有高度挑战性，因为不期望的体内行为，例如快速肾脏清除和当前NIR发射造影剂在背景组织中的高积累。因此，体内肾脏成像仍然严重依赖于高成本的放射成像技术，如正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT），这不仅限制了基础肾脏研究，而且使外科医生在未来进行成像引导的肾脏手术具有挑战性。本申请的目的是通过开发一类肾脏可清除近红外（NIR）发射纳米探针来解决这些关键挑战，这些纳米探针具有高肾脏靶向特异性、可调肾脏保留时间和在正常背景组织和网状内皮系统（RES）器官中的最小累积，从而可以在所需检测时间窗口内以高对比度实现非侵入性和侵入性肾脏成像。

DESCRIPTION In vivo fluorescence imaging, allowing the visualization of physiological processes in an intact living organism, has been an indispensable preclinical tool for fundamental understandings of disease pathology and development. More recently, it has also been translated into clinical trials to improve surgery outcomes and lower health-care costs. However, delivery of in vivo fluorescence imaging into preclinical kidney research and surgery remains highly challenging because of undesired in vivo behaviors such as rapid kidney clearance and high accumulation in background tissues of current NIR emitting contrast agents. As a result, in vivo kidney imaging remains heavily relied on high-cost radiological imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), which not only limits fundamental kidney research but also makes it challenging for surgeons to conduct imaging-guided kidney surgery in the future. The objective of this application to address these critical challenges by developing a class of renal clearable near infrared (NIR) emitting nanoprobes with high kidney-targeting specificity, tunable kidney retention time and minimum accumulation in normal background tissues and reticuloendothelial system (RES) organs, so that both noninvasive and invasive kidney imaging can be achieved at high contrast with desired detection time window.