Fluorescence Imaging of Peripheral Nerves by a Na_v1.7-Targeted Inhibitor Cystine Knot Peptide

Abstract

IgG staining in human vagus nerves; H&E and Na v 1.7 expression in mouse sciatic nerves; tryptic digestion experiments for Hsp1a and Hsp1a-FL; epifluorescence images of sciatic nerves injected with Hsp1a-FL, block, or PBS, and the fluorescence quantification; fresh tissue confocal fluorescence microscopy (PDF) The authors declare the following competing financial interest(s): J.G., P.D.S.F., G.F.K. and T.R. are co-inventors on a Hsp1a-related patent application. S.K. and T.R. are shareholders of Summit Biomedical Imaging, LLC.

Exploiting molecular probes to perform near‐infrared fluorescence‐guided surgery

“…Although the iatrogenic ureteric injury is relatively rare compared to nerve injury, it is difficult to accurately recognize the injury postoperatively, leading to delayed diagnosis and treatment of ureter repair. 118 Prophylactic ureteric stents are utilized in some cases to help identify ureters, but this invasive method remains controversial among surgeons, because the insertion of the catheter may lead to the ureteric injury itself and increase the risk of postoperative urinary complications. 119 Fluorescence-guided discrimination of ureters makes the advantage of minimal invasion, which may contribute to the prevention of iatrogenic ureteric injury.…”

Fluorescence labeling of a NaV1.7-targeted peptide for near-infrared nerve visualization

“…We chose a NIR fluorophore for its emission wavelength with favorable tissue penetration potential for intraoperative applications. We modified Hs1a via nucleophilic substitution as previously described [30]. The synthesis was performed under basic conditions in a mixture of water and acetonitrile, with 14% yield.…”

“…resonance imaging (MRI) and nerve ultrasound [21,22]. However, fluorescent nerve imaging agents [23,24], as well as multimodal optical imaging techniques, are raising interest for intraoperative applications [25][26][27][28][29][30][31][32][33][34][35]. However, the availability of an intraoperative imaging agent that could clearly identify small nerve branches or even larger trunks below the tissue surface, especially in cases of reoperation when normal anatomy is disrupted, could significantly improve surgical precision.…”

Fluorescence labeling of a NaV1.7-targeted peptide for near-infrared nerve visualization

“…We chose a NIR fluorophore for its emission wavelength with favorable tissue penetration potential for intraoperative applications. We modified Hs1a via nucleophilic substitution as previously described [26]. The synthesis was performed under basic conditions in a mixture of water and acetonitrile, with 14% yield.…”

“…Oncologic surgery, in particular, poses a risk of nerve injury as anatomy is often distorted by the disease [10][11][12][13][14][15][16][17]. Tools for pre and perioperative nerve enhancement exist [18][19][20] and fluorescent nerve imaging agents, as well as multimodal optical imaging techniques, are raising interest for intraoperative applications [21][22][23][24][25][26][27][28][29][30][31].…”