Title

A chemically stable fluorescent marker of the ureter.

Document Type

Journal Article

Publication Date

9-1-2018

Journal

Bioorganic & medicinal chemistry letters

Volume

28

Issue

16

Keywords

Fluorescence-guided surgery; Fluorophore synthesis; Near-IR fluorescence

Abstract

Surgical methods guided by exogenous fluorescent markers have the potential to define tissue types in real time. Small molecule dyes with efficient and selective renal clearance could enable visualization of the ureter during surgical procedures involving the abdomen and pelvis. These studies report the design and synthesis of a water soluble, net neutral C4'-O-alkyl heptamethine cyanine, Ureter-Label (UL)-766, with excellent properties for ureter visualization. This compound is accessed through a concise synthetic sequence involving an N- to O-transposition reaction that provides other inaccessible C4'-O-alkyl heptamethine cyanines. Unlike molecules containing a C4'-O-aryl substituent, which have also been used for ureter visualization, UL-766 is not reactive towards glutathione and the cellular proteome. In addition, rat models of abdominal surgery reveal that UL-766 undergoes efficient and nearly exclusive renal clearance in vivo. In total, this molecule represents a promising candidate for visualizing the ureter during a variety of surgical interventions.

Peer Reviewed

1

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