title: Tailored near-infrared contrast agents for image guided surgery.
abstract: The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge.
authors.affiliation: †Department of Chemistry, Center for Diagnostics and Therapeutics and The Center for Biotechnology and Drug Design, Georgia State University, 100 Piedmont Road SE, Atlanta, Georgia 30303, United States.
authors.forename: Costyl N
authors.initials: CN
authors.lastname: Njiojob
authors.affiliation: †Department of Chemistry, Center for Diagnostics and Therapeutics and The Center for Biotechnology and Drug Design, Georgia State University, 100 Piedmont Road SE, Atlanta, Georgia 30303, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Owens
authors.affiliation: †Department of Chemistry, Center for Diagnostics and Therapeutics and The Center for Biotechnology and Drug Design, Georgia State University, 100 Piedmont Road SE, Atlanta, Georgia 30303, United States.
authors.forename: Lakshminarayana
authors.initials: L
authors.lastname: Narayana
authors.affiliation: ‡Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, United States.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: ‡Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, United States.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: †Department of Chemistry, Center for Diagnostics and Therapeutics and The Center for Biotechnology and Drug Design, Georgia State University, 100 Piedmont Road SE, Atlanta, Georgia 30303, United States.
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003287:Contrast Media / Q000032:analysis* / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000032:analysis* / Q000493:pharmacokinetics; D007259:Infrared Rays; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000601:surgery; D061848:Optical Imaging / Q000379:methods; D000644:Quaternary Ammonium Compounds / Q000032:analysis* / Q000493:pharmacokinetics; D013451:Sulfonic Acids / Q000032:analysis* / Q000493:pharmacokinetics; D025321:Surgery, Computer-Assisted / Q000379:methods
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D000644:Quaternary Ammonium Compounds; D013451:Sulfonic Acids; C562069:ZW800-1 compound