Kanda Swamy Aravind, Swamy Mahadeva M M, Yuyama Kohei, Jin Takeshi, Monde Kenji
Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
ACS Med Chem Lett. 2025 Jul 18;16(8):1641-1647. doi: 10.1021/acsmedchemlett.5c00310. eCollection 2025 Aug 14.
Fluorescence-guided tumor detection using tumor-targeting imaging agents is critical for achieving complete surgical resection with tumor-free margins. Shortwave infrared (SWIR, 900-1400 nm) fluorescence imaging enables deeper tissue penetration due to reduced tissue autofluorescence and scattering relative to conventional visible (400-700 nm) and near-infrared (NIR, 700-900 nm) imaging. In this study, a series of estrogen receptor (ER)-targeting imaging probes were developed by conjugating the anticancer drug-based ligand tamoxifen (TAM) with the FDA-approved indocyanine green (ICG), yielding ICG-TAM and its π-conjugated extended analogues, ICG-C9-TAM and ICG-C11-TAM. Although ICG-TAM exhibits peak absorption and emission in the NIR region, it also emits in the SWIR region. ICG-C9-TAM and ICG-C11-TAM were further evaluated for noninvasive SWIR fluorescence imaging. SWIR fluorescence imaging was performed in ER-expressing cervical and breast cancer cells using the TAM conjugates. These findings support the use of receptor-targeted ligands for specific biomolecular imaging in ER-positive cancer models.
使用肿瘤靶向成像剂进行荧光引导的肿瘤检测对于实现具有无肿瘤切缘的完整手术切除至关重要。与传统的可见光（400 - 700 nm）和近红外（NIR，700 - 900 nm）成像相比，短波红外（SWIR，900 - 1400 nm）荧光成像由于组织自发荧光和散射减少，能够实现更深的组织穿透。在本研究中，通过将基于抗癌药物的配体他莫昔芬（TAM）与FDA批准的吲哚菁绿（ICG）偶联，开发了一系列雌激素受体（ER）靶向成像探针，得到ICG - TAM及其π共轭扩展类似物ICG - C9 - TAM和ICG - C11 - TAM。尽管ICG - TAM在近红外区域表现出峰值吸收和发射，但它也在短波红外区域发射。对ICG - C9 - TAM和ICG - C11 - TAM进行了进一步的无创短波红外荧光成像评估。使用TAM偶联物在表达ER的宫颈癌细胞和乳腺癌细胞中进行了短波红外荧光成像。这些发现支持在ER阳性癌症模型中使用受体靶向配体进行特异性生物分子成像。
