Surface chemistry for high-contrast fluorescence kidney imaging

高对比度荧光肾脏成像的表面化学

• 批准号: 8753250
• 负责人: Jie Zheng
• 金额: $ 34.04万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753250
• 关键词: Address; Adsorption; Adult; Behavior; Biocompatible; Blood; Blood flow; Caliber; Cardiac Output; Charge; Chemistry; Clinical Trials; Contrast Media; Detection; Development; Disease; Engineering; Exhibits; Fluorescence; Foundations; Future; Glutathione; Gold; Health Care Costs; Hydrophobicity; Image; Imagery; Imaging Techniques; Investigation; Kidney; Kidney Diseases; Kidney Neoplasms; Kinetics; Lead; Life; Ligands; Liver; Molecular; Operative Surgical Procedures; Organ; Organism; Outcome; Pathology; Permeability; Physiological Processes; Plasma; Play; Polyethylene Glycols; Positron-Emission Tomography; Radioactive Tracers; Renal carcinoma; Renal clearance function; Research; Resistance; Reticuloendothelial System; Serum Proteins; Skin; Skin Tissue; Solid; Specificity; Surface; Surgeon; Time; Tissues; Toxic effect; Translating; United States; Urinary system; Work; clinical practice; cost; disease diagnosis; drug development; fluorescence imaging; fluorophore; imaging probe; improved; in vivo; kidney imaging; kidney surgery; meetings; mouse model; nanoparticle; nanoprobe; nanotoxicity; pre-clinical; public health relevance; single photon emission computed tomography; success; tool; tumor; uptake

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.

体内荧光成像，允许在一个完整的活生物体的生理过程可视化，已经成为一个必不可少的临床前工具，基本了解疾病病理和发展。最近，它还被转化为临床试验，以改善手术效果和降低医疗保健成本。然而，将体内荧光成像技术应用于临床前肾脏研究和手术仍然具有很大的挑战性，因为目前的近红外造影剂在体内的行为不理想，比如肾脏的快速清除和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），这不仅限制了肾脏的基础研究，也给外科医生在未来进行成像引导的肾脏手术带来了挑战。本应用程序的目的是通过开发一类肾清除近红外（NIR）发射纳米探针来解决这些关键挑战，该探针具有高肾脏靶向特异性，可调节肾脏保留时间，并且在正常背景组织和网状内皮系统（RES）器官中积累最少，因此无创和有创肾脏成像可以在高对比度下实现所需的检测时间窗。