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Randomized Controlled Trial
. 2019 Jul 16;10(1):3118.
doi: 10.1038/s41467-019-11014-1.

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

Kim S de Valk  1   2 , Henricus J Handgraaf  3 , Marion M Deken  3 , Babs G Sibinga Mulder  3 , Adrianus R Valentijn  3 , Anton G Terwisscha van Scheltinga  3 , Joeri Kuil  3 , Michiel J van Esdonk  4 , Jaap Vuijk  3 , Rob F Bevers  3 , Koen C Peeters  3 , Fabian A Holman  3 , John V Frangioni  5 , Jacobus Burggraaf  4 , Alexander L Vahrmeijer  3
Affiliations
Randomized Controlled Trial

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

Kim S de Valk et al. Nat Commun. .

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.

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Conflict of interest statement

J.V.F. is founder and CEO of Curadel, LLC, a for-profit company marketing the FLARE® technology platform for NIR fluorescence-guided surgery. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
High sensitivity detection of ZW800-1 near-infrared (NIR) fluorescence in patients using three different commercial imaging systems. Invisible NIR fluorescence of ZW800-1 is pseudo-colored in green and overlayed in real-time onto the anatomical images
Fig. 2
Fig. 2
Ureter residing under peritoneum. The ureter (dashed circle) is captured during a pulse of urine flow during surgery. The darker green areas in the near-infrared (NIR) fluorescence image (small arrows) is background fluorescence caused by the vessels in the surrounding tissue. The images were acquired using the Olympus® imaging system during laparoscopic surgery
Fig. 3
Fig. 3
Signal-to-background ratio (SBR) of the ureter. Note: the SBR of 5.0 mg is significantly lower than the SBR of 2.5 mg (unequal variance t test: p = 0.003) and 1.0 mg (unequal variance t test: p = 0.01) in the first hour post dose. The values represent the mean ± SD (n = 4 patients each group). Source data are provided as a Source Data file
Fig. 4
Fig. 4
Functional assessment of ureter flow and patency with ZW800-1 (acquired using the Olympus® imaging system)
See this image and copyright information in PMC

References

    1. Vahrmeijer AL, Hutteman M, van der Vorst JR, van de Velde CJ, Frangioni JV. Image-guided cancer surgery using near-infrared fluorescence. Nat. Rev. Clin. Oncol. 2013;10:507–518. doi: 10.1038/nrclinonc.2013.123. - DOI - PMC - PubMed
    1. Choi HS, et al. Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat. Biotechnol. 2013;31:148–153. doi: 10.1038/nbt.2468. - DOI - PMC - PubMed
    1. Choi HS, et al. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angew. Chem. Int. Ed. Engl. 2011;50:6258–6263. doi: 10.1002/anie.201102459. - DOI - PMC - PubMed
    1. Hyun H, et al. 700-nm Zwitterionic near-infrared fluorophores for dual-channel image-guided surgery. Mol. Imaging Biol. 2016;18:52–61. doi: 10.1007/s11307-015-0870-4. - DOI - PMC - PubMed
    1. Hyun H, et al. cGMP-compatible preparative scale synthesis of near-infrared fluorophores. Contrast Media Mol. Imaging. 2012;7:516–524. doi: 10.1002/cmmi.1484. - DOI - PMC - PubMed

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