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

被引：57

作者：

de Valk, Kim S. ^{[1
,2
]}

Handgraaf, Henricus J. ^{[2
]}

Deken, Marion M. ^{[2
]}

Mulder, Babs G. Sibinga ^{[2
]}

Valentijn, Adrianus R. ^{[2
]}

van Scheltinga, Anton G. Terwisscha ^{[2
]}

Kuil, Joeri ^{[2
]}

van Esdonk, Michiel J. ^{[1
]}

Vuijk, Jaap ^{[2
]}

Bevers, Rob F. ^{[2
]}

Peeters, Koen C. ^{[2
]}

Holman, Fabian A. ^{[2
]}

Frangioni, John, V ^{[3
]}

Burggraaf, Jacobus ^{[1
]}

Vahrmeijer, Alexander L. ^{[2
]}

机构：

[1] Ctr Human Drug Res, Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Leiden, Netherlands

[3] Curadel LLC, Marlborough, MA USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

FLUORESCENCE-GUIDED IDENTIFICATION; INDOCYANINE GREEN; CANCER-SURGERY; INJURY;

D O I：

10.1038/s41467-019-11014-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：6

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