Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.
Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.
复制标题
使用现有的临床荧光成像系统，通过近红外神经特异性荧光团实现保留神经的妇科手术。
DOI：
10.1002/smll.202300011
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Gibbs,SummerL
中科院分区：
文献类型：
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作者：
Barth,ConnorW;Rizvi,SyedZakiHusain;Masillati,AnasM;Chakraborty,Samrat;Wang,LeiG;Montaño,AntonioR;Szafran,DaniA;Greer,WilliamS;vandenBerg,NynkeS;Sorger,Jonathan;Rao,DeepaA;Alani,AdamWG;Gibbs,SummerL
接受妇科手术的患者由于术中神经损伤而遭受持久的副作用。女性盆腔神经解剖结构中细小、脆弱的神经具有复杂和不均匀的分支模式，使得在标准的妇科手术（如子宫切除术、膀胱切除术和结直肠癌切除术）中神经保留努力变得困难，因此许多患者留下了尿失禁和性功能障碍。本文研制了一种近红外（NIR）荧光神经特异性造影剂LGW08‐35，该造影剂与临床荧光引导手术（FGS）系统在光谱上兼容，可快速应用于妇科手术。研究了胶束配方LGW08‐35的毒理学、药代动力学（PK）和药效学（PD），从而确定了最佳成像剂量和时间点、血液和组织摄取参数以及最大耐受剂量（MTD）。将配方荧光团应用于雌性大鼠和猪盆腔神经解剖成像，验证了持续的临床翻译和实时识别重要神经（如股神经、坐骨神经、腰椎神经、髂神经和腹下神经）的使用。LGW08‐35临床应用的进一步开发将为外科医生直接可视化重要神经提供有价值的工具，并有助于持续表征女性盆腔神经解剖学，以消除妇科手术中神经损伤的衰弱副作用。
Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve‐sparing efforts during standard gynecological procedures such as hysterectomy, cystectomy, and colorectal cancer resection difficult, and thus many patients are left with incontinence and sexual dysfunction. Herein, a near‐infrared (NIR) fluorescent nerve‐specific contrast agent, LGW08‐35, that is spectrally compatible with clinical fluorescence guided surgery (FGS) systems is formulated and characterized for rapid implementation for nerve‐sparing gynecologic surgeries. The toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) of micelle formulated LGW08‐35 are examined, enabling the determination of the optimal imaging doses and time points, blood and tissue uptake parameters, and maximum tolerated dose (MTD). Application of the formulated fluorophore to imaging of female rat and swine pelvic neuroanatomy validates the continued clinical translation and use for real‐time identification of important nerves such as the femoral, sciatic, lumbar, iliac, and hypogastric nerves. Further development of LGW08‐35 for clinical use will unlock a valuable tool for surgeons in direct visualization of important nerves and contribute to the ongoing characterization of the female pelvic neuroanatomy to eliminate the debilitating side effects of nerve damage during gynecological procedures.