Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model

被引：15

作者：

Friedman-Levi Y. ^{[1
]}

Larush L. ^{[2
]}

Diana M. ^{[3
]}

Marchegiani F. ^{[3
]}

Marescaux J. ^{[3
]}

Goder N. ^{[4
]}

Lahat G. ^{[4
]}

Klausner J. ^{[4
]}

Eyal S. ^{[1
,5
]}

Magdassi S. ^{[2
]}

Nizri E. ^{[4
]}

机构：

[1] Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem

[2] Casali Institute for Applied Chemistry, The Hebrew University of Jerusalem, Jerusalem

[3] IHU-Strasbourg, Institute of Image-Guided Surgery, 1, place de l’Hôpital, Strasbourg

[4] Laboratory of Surgical Oncology, Division of Surgery, Department of Surgery A, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv

[5] David R. Bloom Centre for Pharmacy and Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology, Therapeutics at, The Hebrew University of Jerusalem, Jerusalem

来源：

Surgical Endoscopy | 2018年 / 32卷 / 2期

关键词：

Indocyanine green; Liposomes; Minimal invasive surgery; Ureteral injury;

D O I：

10.1007/s00464-017-5773-9

中图分类号：

学科分类号：

摘要：

Background: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. Methods: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). Results: The optimal liposomal ICG loading dose was 20%, for the different liposomes’ sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. Conclusions: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments. © 2017, Springer Science+Business Media, LLC.

引用

页码：963 / 970

页数：7

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