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Design of a Near Infrared Fluorescent Ureter Imaging Agent for Prevention of Ureter Damage during Abdominal Surgeries
Authors:Sakkarapalayam M Mahalingam  Karson S Putt  Madduri Srinivasarao  Philip S Low
Institution:1.Department of Chemistry, PSG College of Arts and Science and PSG Institute of Advanced Studies, Coimbatore 641004, Tamil Nadu, India;2.Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA;3.Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA;
Abstract:The inadvertent severing of a ureter during surgery occurs in as many as 4.5% of colorectal surgeries. To help prevent this issue, several near-infrared (NIR) dyes have been developed to assist surgeons with identifying ureter location. However, the majority of these dyes exhibit at least some issue that precludes their widespread usage such as high levels of uptake in other tissues, overlapping emission wavelengths with other NIR dyes used for other fluorescence-guided surgeries, and/or rapid excretion times through the ureters. To overcome these limitations, we have synthesized and characterized the spectral properties and biodistribution of a new series of PEGylated UreterGlow derivatives. The most promising dye, UreterGlow-11 was shown to almost exclusively excrete through the kidneys/ureters with detectable fluorescence observed for at least 12 h. Additionally, while the excitation wavelength is similar to that of other NIR dyes used for cancer resections, the emission is shifted by ~30 nm allowing for discrimination between the different fluorescence-guided surgery probes. In conclusion, these new UreterGlow dyes show promising optical and biodistribution characteristics and are good candidates for translation into the clinic.
Keywords:ureter imaging  fluorescence-guided surgery  near-infrared dye  PEG pharmacokinetics
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