Centre for Human Drug Research, Leiden, The Netherlands.
Leiden University Medical Center, Leiden, The Netherlands.
Nat Commun. 2019 Jul 16;10(1):3118. 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.
医源性输尿管损伤是腹部手术的一种可怕并发症。两性离子近红外荧光团是一种具有几何平衡、电中性表面电荷的分子，这导致了肾脏特异性清除和超低非特异性背景结合。这类分子可以通过提供实时解剖和功能成像，甚至在完整的腹膜下，解决输尿管定位问题。本文首次报道了该化学类别的人体经验，以及在接受腹腔镜腹部骨盆手术的患者中的疗效研究。两性离子近红外荧光团 ZW800-1 是安全的，具有与理想血池造影剂一致的药代动力学特性，并且在单次低剂量静脉注射后迅速排泄到尿液中。在 ZW800-1 注射后几分钟内开始观察输尿管的结构和功能，并持续数小时。两性离子近红外荧光团在腹腔镜腹部骨盆手术中增加了价值，并可能减少医源性尿道损伤。此外，ZW800-1 设计为一步共价连接性，为开发新型靶向配体创造了可能性。
