Kong Chenyang, Wang Xiaohui, Yu Jintao, Wen Li, Zheng Chengwen, Yin Ge, Xu Kai, He Weiwei, Wang Hao, Lan Xiaoli, Jiang Dawei, Sun Yu
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Adv Sci (Weinh). 2025 Aug;12(29):e04464. doi: 10.1002/advs.202504464. Epub 2025 May 19.
For patients with severe and profound hearing loss, cochlear implant (CI), a common and effective modality for restoring hearing, directly stimulates spiral ganglion neurons (SGNs) to generate electrical activity and form auditory perception. However, the postoperative outcome of CI is significantly influenced by the number of surviving SGNs, which is a key focus of preoperative evaluation. Existing audiologic function and radiographic tests cannot directly demonstrate the integrity of inner ear primary neurons. In this study, we developed and validated a radionuclide-labeled anti-vesicular glutamate transporter 1 (anti-VGLUT1) antibody-drug and achieved animal-level in vivo imaging of cochlear SGNs using nuclear imaging. By screening the public single-cell sequencing database, it is found that VGLUT1 can serve as a representative cell membrane marker for SGN in the cochlea. The potential of anti-VGLUT1 conjugated to the long half-life Lu as a molecular probe to detect the relative number of SGNs in SGN-injured mouse and pig models is explored. The study provides a novel method for assessing cochlear nerve integrity in vivo by visualizing target antigen expression levels through nuclear imaging. This approach is promising to help CI candidates with preoperative inner ear SGN integrity assessment, contributing to clinical decision-making.
对于重度和极重度听力损失患者,人工耳蜗植入(CI)是恢复听力的一种常见且有效的方式,它直接刺激螺旋神经节神经元(SGNs)产生电活动并形成听觉感知。然而,CI的术后效果受到存活SGNs数量的显著影响,这是术前评估的关键重点。现有的听力学功能和影像学检查无法直接显示内耳初级神经元的完整性。在本研究中,我们开发并验证了一种放射性核素标记的抗囊泡谷氨酸转运体1(anti-VGLUT1)抗体药物,并利用核成像实现了耳蜗SGNs的动物水平体内成像。通过筛选公共单细胞测序数据库,发现VGLUT1可作为耳蜗中SGN的代表性细胞膜标记物。探索了用半衰期长的镥标记的anti-VGLUT1作为分子探针检测SGN损伤小鼠和猪模型中SGNs相对数量的潜力。该研究通过核成像可视化靶抗原表达水平,为体内评估耳蜗神经完整性提供了一种新方法。这种方法有望帮助人工耳蜗植入候选者进行术前内耳SGN完整性评估,有助于临床决策。