Biomedical Engineering Department, Oregon Health and Science University, Portland, OR, 97201, USA.
Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA.
Adv Mater. 2024 Apr;36(16):e2304724. doi: 10.1002/adma.202304724. Epub 2023 Dec 18.
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, it is shown 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 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 surgical workflow, paving the path for clinical translation to reduce morbidity from nerve injury for prostate cancer patients.
荧光引导手术（FGS）有望通过近红外（NIR）荧光团为组织和疾病特异性对比带来手术医学的革命。临床开放式和腹腔镜 FGS 视觉系统几乎专门在 NIR 波长下运行。然而，与临床可用成像系统兼容的组织特异性近红外对比剂仍然缺乏，这使得在前列腺切除术中识别神经组织仍然是一个持续的挑战。在这里，通过将类似药物的分子设计概念和荧光团化学相结合，成功地生产了一系列用于术中神经特异性成像的基于 NIR 呫吨的荧光团。该候选物在犬的前列腺和猪的髂丛中使用已经广泛用于微创前列腺切除术的临床达芬奇手术系统，很容易地描绘出了前列腺神经。这些结果证明了 NIR 神经结合荧光团的分子工程的可行性，以便于整合到现有的手术工作流程中，为临床转化铺平了道路，以降低前列腺癌患者因神经损伤导致的发病率。
