A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery

• Published in: Nature communications Vol. 10; no. 1; pp. 3118 - 6
• Main Authors: de Valk, Kim S., Handgraaf, Henricus J., Deken, Marion M., Sibinga Mulder, Babs G., Valentijn, Adrianus R., Terwisscha van Scheltinga, Anton G., Kuil, Joeri, van Esdonk, Michiel J., Vuijk, Jaap, Bevers, Rob F., Peeters, Koen C., Holman, Fabian A., Frangioni, John V., Burggraaf, Jacobus, Vahrmeijer, Alexander L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/2779/109; 692/698/1864/1861; 692/700/1421; 692/700/565/545; Adolescent; Adult; Aged; Chemical compounds; Female; Fluorescence; Fluorescent Dyes - administration & dosage; Fluorescent Dyes - adverse effects; Fluorescent Dyes - pharmacokinetics; Fluorophores; Healthy Volunteers; Humanities and Social Sciences; Humans; I.R. radiation; Infusions, Intravenous; Injection; Intraoperative Complications - etiology; Intraoperative Complications - prevention & control; Intravenous administration; Ionophores - administration & dosage; Ionophores - adverse effects; Ionophores - pharmacokinetics; Laparoscopy; Laparoscopy - adverse effects; Laparoscopy - methods; Male; Mapping; Middle Aged; multidisciplinary; Near infrared radiation; Optical Imaging - methods; Organic chemistry; Peritoneum; Pharmacology; Quaternary Ammonium Compounds - administration & dosage; Quaternary Ammonium Compounds - adverse effects; Quaternary Ammonium Compounds - pharmacokinetics; Real time; Science; Science (multidisciplinary); Spectroscopy, Near-Infrared - methods; Structure-function relationships; Sulfonic Acids - administration & dosage; Sulfonic Acids - adverse effects; Sulfonic Acids - pharmacokinetics; Surface charge; Surgery; Ureter; Ureter - diagnostic imaging; Ureter - injuries; Urine; Young Adult; Zwitterions
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11014-1

Iatrogenic injury of the ureters is a feared complication of abdominal surgery. Zwitterionic near-infrared fluorophores are molecules with geometrically-balanced, electrically-neutral surface charge, which leads to renal-exclusive clearance and ultralow non-specific background binding. Such molecules could solve the ureter mapping problem by providing real-time anatomic and functional imaging, even through intact peritoneum. Here we present the first-in-human experience of this chemical class, as well as the efficacy study in patients undergoing laparoscopic abdominopelvic surgery. The zwitterionic near-infrared fluorophore ZW800-1 is safe, has pharmacokinetic properties consistent with an ideal blood pool agent, and rapid elimination into urine after a single low-dose intravenous injection. Visualization of structure and function of the ureters starts within minutes after ZW800-1 injection and lasts several hours. Zwitterionic near-infrared fluorophores add value during laparoscopic abdominopelvic surgeries and could potentially decrease iatrogenic urethral injury. Moreover, ZW800-1 is engineered for one-step covalent conjugatability, creating possibilities for developing novel targeted ligands. Iatrogenic injury of the ureters is a feared complication of laparoscopic abdominal surgery. Here the authors present the NIR fluorophore ZW800-1 as an intraoperative imaging agent for ureter mapping, showing its safety, pharmacokinetic properties, and efficacy in healthy volunteers and patients undergoing abdominopelvic surgery.