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.
One in 10 adults in the United States suffers from a variety of kidney diseases; thus developing low- cost and high-sensitivity imaging techniques that can advance our fundamental understandings of underlying mechanisms of kidney diseases and drug development will be highly desired but remains highly challenging. We aim to develop a new class of near infrared (NIR)-emitting nanoparticles with desired in vivo behaviors that can significantly enhance kidney-imaging contrast more than one order of magnitude over current fluorescent contrast agents while allow imaging-time window to be optimized for different imaging requirements. Success of the proposed work will enable in vivo fluorescence imaging to serve as a practical tool to promote preclinical kidney research and catalyze new paradigm shifts in imaging guided kidney surgery. 1
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