sNIR: A novel NIR dye for precision fluorescence-guided surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article sNIR: A novel NIR dye for precision fluorescence-guided surgery Oliver Bruns, Merle Weitzenberg, Gina Fürtjes, Martin Ullrich, and 32 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8406889/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Complete removal of tumors during surgery is essential to minimizing the risk of recurrence, and labeling tumors so that they fluoresce at near-infrared wavelengths can assist surgeons in detecting residual neoplastic tissue intraoperatively. Fluorescent contrast agents currently under clinical investigation are often not cancer cell-specific and suffer from non-specific retention. This drastically compromises tumor-to-background contrast ratios and, thus, the detection of small tumor lesions. Here, we report a novel cyanine dye, “sNIR,” which mediates faster excretion and reduced non-specific binding compared to the commercially available benchmark IRDye800. When conjugated to validated ligands of tumor-associated cell surface markers, only sNIR-based contrast agents enabled high-contrast tumor imaging in murine models. To exemplify sNIR's clinical potential, we focused on meningioma resection - a clinical challenge where microscopic tumor remnants left in the resection bed drive recurrence. Our probe “TATE-sNIR” specifically targets somatostatin receptor subtype 2 (SSTR2), reliably overexpressed in meningiomas. TATE-sNIR binds the target receptor tightly and specifically in vitro and in vivo, enabling clean receptor-mediated imaging in healthy mice and in mice bearing ectopic or orthotopic meningiomas or ectopic pheochromocytomas. A proof-of-concept study in healthy pigs demonstrated the accumulation of TATE-sNIR in the pituitary gland, an expected target organ. The signal was strong enough to be detectable by clinical exoscopes with near-infrared fluorescence imaging capabilities, underscoring TATE-sNIR’s translational potential. With its high labeling precision and efficiency, TATE sNIR holds great potential to visualize microscopic meningioma tumor remnants too small to be detected using the current standard of practice, even during extended surgeries. Health sciences/Oncology/Surgical oncology Biological sciences/Drug discovery/Diagnostics Biological sciences/Biological techniques/Imaging/Optical imaging Biological sciences/Cancer/Cancer imaging Health sciences/Medical research/Translational research Full Text Additional Declarations Yes there is potential Competing Interest. Oliver Plettenburg, Merle Marie Weitzenberg, Gina Fürtjes, Bernardo Assein Arús, and Volker Neuschmelting have filed a patent application for the sNIR dye and its conjugates (European Patent Application WO 2023/227601 A1). We have no financial interest to disclose. Supplementary Files 20251219sNIRSI.pdf Supplementary Materials for sNIR: A novel NIR dye for precision fluorescence-guided surgery Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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