151. A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery
- Author
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Marion M. Deken, Babs G. Sibinga Mulder, Fabian A. Holman, Michiel J van Esdonk, Jacobus Burggraaf, Anton G. T. Terwisscha van Scheltinga, Alexander L. Vahrmeijer, Adrianus R. P. M. Valentijn, Henricus J.M. Handgraaf, Kim S. de Valk, John V. Frangioni, Koen C.M.J. Peeters, Rob F. M. Bevers, Joeri Kuil, and Jaap Vuijk
- Subjects
Male ,0301 basic medicine ,Urethral injury ,Blood pool agent ,General Physics and Astronomy ,02 engineering and technology ,chemistry.chemical_compound ,Clinical trials ,Medicine ,Infusions, Intravenous ,Intraoperative Complications ,lcsh:Science ,Spectroscopy, Near-Infrared ,Multidisciplinary ,Iatrogenic injury ,Optical Imaging ,Middle Aged ,021001 nanoscience & nanotechnology ,Healthy Volunteers ,3. Good health ,medicine.anatomical_structure ,Female ,Medical imaging ,0210 nano-technology ,Efficacy Study ,Adult ,medicine.medical_specialty ,Fluorophore ,Adolescent ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,Ureter ,Humans ,In patient ,Aged ,Fluorescent Dyes ,Ionophores ,business.industry ,General Chemistry ,Surgery ,Quaternary Ammonium Compounds ,030104 developmental biology ,chemistry ,Laparoscopy ,lcsh:Q ,Sulfonic Acids ,business ,Abdominal surgery - Abstract
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.
- Published
- 2019