Theranostics 2015; 5(1):1-11. doi:10.7150/thno.10259

Research Paper

Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery

Hideyuki Wada1,2, Hoon Hyun1, Christina Vargas1,3, Julien Gravier1,4, GwangLi Park1, Sylvain Gioux1, John V. Frangioni1,5,6, Maged Henary7✉, Hak Soo Choi1,8✉

1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
3. Division of Plastic and Reconstructive Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215.
4. INSERM, CRI, U823, Institut Albert Bonniot, 38042 Grenoble, France.
5. Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
6. Curadel, LLC, 377 Plantation Street, Worcester, MA 01605.
7. Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303.
8. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, South Korea.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wada H, Hyun H, Vargas C, Gravier J, Park G, Gioux S, Frangioni JV, Henary M, Choi HS. Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery. Theranostics 2015; 5(1):1-11. doi:10.7150/thno.10259. Available from http://www.thno.org/v05p0001.htm

File import instruction

Abstract

Objective: 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.

Design: 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.

Results: 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.

Conclusion: 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.

Keywords: Pancreas-related complications, Postoperative pancreatic fistula, Intraoperative pancreatic injury, Image-guided surgery, Near-Infrared fluorescence.