A clinically relevant formulation for direct administration of nerve specific fluorophores to mitigate iatrogenic nerve injury

Barth, Connor W.; Shah, Vidhi; Wang, Lei G.; Masillati, Anas M; Fatease, Adel Al; Rizvi, Syed Zaki Husain; Antaris, Alexander L.; Sorger, Jonathan M.; Rao, Deepa; Alani, Adam W.G.; Gibbs, Summer L.

doi:10.1016/j.biomaterials.2022.121490

Cited by 12 publications

(8 citation statements)

References 68 publications

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“…[ 26 ] We recently developed a hydrogel‐based formulation for nerve‐specific small molecules that can be topically applied as a liquid followed by rapid gelling for tissue hold upon contact. [ 21 ] This application approach is fully compatible with minimally invasive prostatectomy, where the cold‐cutting technique is routinely used instead of electrocauterization to prevent thermal damage to the neurovascular bundle. While this surgical technique prevents thermal nerve damage, it results in increased surgical site bleeding, making white light‐guided nerve tissue identification and preservation more challenging.…”

Section: Discussionmentioning

confidence: 99%

Nerve Visualization using Phenoxazine‐Based Near‐Infrared Fluorophores to Guide Prostatectomy

Wang,

Montaño,

Masillati

et al. 2023

Advanced Materials

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Fluorescence‐guided surgery (FGS) is poised to revolutionize surgical medicine through near‐infrared (NIR) fluorophores for tissue‐ and disease‐specific contrast. Clinical open and laparoscopic FGS vision systems operate nearly exclusively at NIR wavelengths. However, tissue‐specific NIR contrast agents compatible with clinically available imaging systems are lacking, leaving nerve tissue identification during prostatectomy a persistent challenge. Here, we show that combining drug‐like molecular design concepts and fluorophore chemistry enabled the production of a library of NIR phenoxazine‐based fluorophores for intraoperative nerve‐specific imaging. The lead candidate readily delineated prostatic nerves in the canine and iliac plexus in the swine models using the clinical da Vinci Surgical System that has been popularized for minimally invasive prostatectomy procedures. These results demonstrate the feasibility of molecular engineering of NIR nerve‐binding fluorophores for ready integration into the existing surigical workflow, paving the path for clinical translation to reduce morbidity from nerve injury for prostate cancer patients.This article is protected by copyright. All rights reserved

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Section: Discussionmentioning

confidence: 99%

Nerve Visualization using Phenoxazine‐Based Near‐Infrared Fluorophores to Guide Prostatectomy

Wang,

Montaño,

Masillati

et al. 2023

Advanced Materials

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“…By adjusting the conjugation of agents such as oxazines 1 and 4, Dr. Gibbs’ group has been able to create nerve-specific fluorophores that emit closer to 700 and 800 nm, which allow these agents to remain compatible with current clinical fluorescence imaging systems. 55 …”

Section: Normal Tissue Dyesmentioning

confidence: 99%

“…By adjusting the conjugation of agents such as oxazines 1 and 4, Dr. Gibbs' group has been able to create nerve-specific fluorophores that emit closer to 700 and 800 nm, which allow these agents to remain compatible with current clinical fluorescence imaging systems. 55 Currently, Dr. Gibbs' group is moving one of their lead 700-nm nerve probes, LGW16-03, toward clinical translation. The group has studied LGW16-03 extensively in rats and mice, and the probe has shown a promising SBR when highlighting human nerves in patients who have undergone lower limb amputations in collaboration with Dr. Eric Henderson.…”

Section: Near-infrared Nerve-specific Probes For Intraoperative Nerve...mentioning

confidence: 99%

“…Dr. Gibbs’ group has been working to chemically modify oxazine 4 to maintain its nerve specificity while shifting its emission into the NIR (650 to 900 nm) spectrum for surgical application. By adjusting the conjugation of agents such as oxazines 1 and 4, Dr. Gibbs’ group has been able to create nerve-specific fluorophores that emit closer to 700 and 800 nm, which allow these agents to remain compatible with current clinical fluorescence imaging systems 55 …”

Section: Normal Tissue Dyesmentioning

confidence: 99%

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Intraoperative molecular imaging: 3rd biennial clinical trials update

Bou-Samra,

Muhammad,

Chang

et al. 2023

J. Biomed. Opt.

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. Significance This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery. Aim National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed. Approach Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center’s third clinical trials update on IMI were selected to discuss their clinical trials and endpoints. Results Dyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed. Conclusions IMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.

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“…Local staining produced a similar neuronal signal to systemic treatment after 1 to 5 minutes (SBR > 2). 129 This improved drug delivery method makes it possible for more relevant probes to be clinically translated for imaging-guided treatments.…”

Section: Route Of Administrationmentioning

confidence: 99%