Hoon Hyun1, Maged Henary2, Tielong Gao3, Lakshminarayana Narayana3, Eric A Owens3, Jeong Heon Lee1, GwangLi Park1, Hideyuki Wada1, Yoshitomo Ashitate1, John V Frangioni1,4, Hak Soo Choi5,6. 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA. 2. Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA. mhenary1@gsu.edu. 3. Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA. 4. Curadel, LLC, 377 Plantation Street, Worcester, MA, 01605, USA. 5. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA. hchoi@bidmc.harvard.edu. 6. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 609-735, South Korea. hchoi@bidmc.harvard.edu.
Abstract
PURPOSE: The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery. PROCEDURES: Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging. RESULTS: ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients ≥199,000 M(-1) cm(-1), emission ≥660 nm, and stability ≥99 % after 24 h in warm serum. In mice, rats, and pigs, ≥80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE® imaging system. CONCLUSIONS: Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.
PURPOSE: The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery. PROCEDURES: Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging. RESULTS:ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients ≥199,000 M(-1) cm(-1), emission ≥660 nm, and stability ≥99 % after 24 h in warm serum. In mice, rats, and pigs, ≥80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE® imaging system. CONCLUSIONS: Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.
Entities:
Keywords:
Image-guided surgery; Near-infrared fluorescence; Optical imaging; Signal-to-background ratio
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