Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery

• Published in: Theranostics 2015, Vol.5 (1), p.1-11
• Main Authors: Wada, Hideyuki, Hyun, Hoon, Vargas, Christina, Gravier, Julien, Park, GwangLi, Gioux, Sylvain, Frangioni, John V, Henary, Maged, Choi, Hak Soo
• Format: Article
• Language: English
• Subjects: Adrenal Glands - metabolism; Animals; Fluorescent Dyes - pharmacokinetics; Kidney - metabolism; Lymph Nodes - metabolism; Male; Mice; Optical Imaging - methods; Pancreas - metabolism; Rats, Sprague-Dawley; Research Paper; Spectroscopy, Near-Infrared - methods; Staining and Labeling - methods; Surgery, Computer-Assisted - methods; Swine; Time Factors
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.10259

Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury. After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands. T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time. Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.