将 GnRH-A 重新用作近红外荧光探针,用于乳腺癌肿瘤和转移的诊断和手术导航。
Repurposing GnRH-A as a Near-Infrared Fluorescent Probe for Diagnosis and Surgical Navigation of Breast Cancer Tumors and Metastases.
发表日期:2024 Jul 12
作者:
Haoran Xu, Zhuoyi Ye, Xin Gao, Yue Dai, Yang Luo, Zhihao Han, Yueqing Gu
来源:
Cellular & Molecular Immunology
摘要:
乳腺癌是全球女性最常见的癌症,给治疗带来了巨大的挑战。保乳手术 (BCS) 是一种创伤较小、疼痛较小的根治性乳房切除术替代方案,不仅可以保留乳房外观,还可以支持术后功能恢复。然而,准确识别肿瘤、精确描绘边缘和彻底清除转移瘤仍然是复杂的手术挑战,而当前成像技术的局限性(包括肿瘤摄取差和信号对比度低)加剧了这一挑战。为了解决这些挑战,我们的研究开发了一系列 GnRHR 靶向探针 (YQGN-n),通过药物重新定位策略用于乳腺癌的荧光成像和手术导航。值得注意的是,YQGN-7 具有高细胞亲和力(Kd 为 217.8 nM),对乳腺癌肿瘤表现出卓越的选择性和特异性,在肿瘤摄取和药代动力学特性方面超越了 ICG 等传统显像剂。此外,YQGN-7 在原发性乳腺肿瘤和转移瘤手术导航中的有效性凸显了其作为 BCS 革命性工具的潜力。
Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast's appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN-n) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity (Kd of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7's effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.