A Biliary Tract-Specific Near-Infrared Fluorescent Dye for Image-Guided Hepatobiliary Surgery
| العنوان: | A Biliary Tract-Specific Near-Infrared Fluorescent Dye for Image-Guided Hepatobiliary Surgery |
|---|---|
| المؤلفون: | So-Hyun Nam, Choonghee Lee, Jung-Man Namgoong, Roger R. Nani, Il Hyung Shin, Martin J. Schnermann, Jaepyeong Cha, Michael Luciano |
| المصدر: | Mol Pharm |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Indocyanine Green, medicine.medical_specialty, Fluorophore, Infrared Rays, Swine, Pharmaceutical Science, 02 engineering and technology, 030226 pharmacology & pharmacy, Palpation, Article, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, medicine, Animals, Hepatectomy, Cholecystectomy, Fluorescent Dyes, medicine.diagnostic_test, Bile duct, business.industry, Optical Imaging, 021001 nanoscience & nanotechnology, Fluorescence, Rats, Hepatobiliary surgery, medicine.anatomical_structure, Surgery, Computer-Assisted, chemistry, Biliary tract, Molecular Medicine, Cystic duct, Administration, Intravenous, Female, Bile Ducts, Radiology, 0210 nano-technology, business, Indocyanine green |
| الوصف: | Despite advances, visual inspection, palpation, and intraoperative ultrasound remain the most utilized tools during surgery today. A particularly challenging issue is the identification of the biliary system due to its complex architecture partially embedded within the liver. Fluorescence guided surgical interventions, particularly using near-infrared (NIR) wavelengths, are an emerging approach for the real-time assessment of the hepatobiliary system. However, existing fluorophores, such as the FDA-approved indocyanine green (ICG), have significant limitations for rapid and selective visualization of bile duct anatomy. Here we report a novel NIR fluorophore, BL (Bile Label)-760, which is exclusively metabolized by the liver providing high signal in the biliary system shortly after intravenous administration. This molecule was identified by first screening a small set of known heptamethine cyanines including clinically utilized agents. After finding that none of these were well-suited, we then designed and tested a small series of novel dyes within a prescribed polarity range. We validated the molecule that emerged from these efforts, BL-760, through animal studies using both rodent and swine models employing a clinically applicable imaging system. In contrast to ICG, BL-760 fluorescence revealed a high target-to-background ratio (TBR) of the cystic duct relative to liver parenchyma 5 min after intravenous injection. During hepatic resection surgery, intrahepatic ducts were clearly highlighted, and bile leakage was easily detected. In conclusion, BL-760 has highly promising properties for intraoperative navigation during hepatobiliary surgery. |
| تدمد: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.9b00453 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fb87bb8275652949402608d2f6c3d5a https://doi.org/10.1021/acs.molpharmaceut.9b00453 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8fb87bb8275652949402608d2f6c3d5a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15438392 15438384 |
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| DOI: | 10.1021/acs.molpharmaceut.9b00453 |