Open AccessA Biliary Tract-Specific Near-Infrared Fluorescent Dye for Image-Guided Hepatobiliary Surgery
Author(s) -
Michael Luciano,
JungMan Namgoong,
Roger R. Nani,
SoHyun Nam,
Choonghee Lee,
Il hyung Shin,
Martin J. Schnermann,
Jaepyeong Cha
Publication year - 2019
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/acs.molpharmaceut.9b00453
Subject(s) - indocyanine green , medicine , bile duct , biliary tract , fluorescence lifetime imaging microscopy , fluorophore , palpation , cystic duct , radiology , fluorescence , pathology , common bile duct , surgery , quantum mechanics , physics
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.