A Biliary Tract-Specific Near-Infrared Fluorescent Dye for Image-Guided Hepatobiliary Surgery
| Autor: | So-Hyun Nam, Choonghee Lee, Jung-Man Namgoong, Roger R. Nani, Il Hyung Shin, Martin J. Schnermann, Jaepyeong Cha, Michael Luciano |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Mol Pharm |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.9b00453 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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