Liu Qingzhu, Qin Shuai, Cai Shuyue, Qiu Ling, Lin Jianguo
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Mol Pharm. 2025 Aug 4;22(8):4844-4854. doi: 10.1021/acs.molpharmaceut.5c00478. Epub 2025 Jul 1.
Triple-negative breast cancer (TNBC) is a serious malignancy characterized by a lack of definitive biomarkers. Research has demonstrated that neuropilin-1 (NRP-1) is highly overexpressed in breast cancer, and its expression levels are strongly associated with the occurrence, development, and prognosis of tumors, thereby positioning NRP-1 as a promising target for the diagnosis and treatment of breast cancer, particularly for TNBC. Herein, NRP-1 was employed as a molecular marker to design and synthesize a PET/NIRF dual-modality molecular probe [F]AmBF-QS-1 for tumor localization and surgical navigation in TNBC. The nonradioactive NIRF probe AmBF-QS-1 was synthesized through the click reaction (chemical purity >95%), and the radioactive probe [F]AmBF-QS-1 was synthesized via the one-step F-labeling method (radiochemical purity >95%, radiochemical yield >15%). The fluorescence imaging, flow cytometry, and cellular uptake studies in cancer cells with different NRP-1 expression levels were performed to verify the specificity of the probe. PET and NIRF imaging of MDA-MB-231 xenografts demonstrated excellent specificity of [F]AmBF-QS-1 for tumor uptake (8.41 ± 0.86%ID/mL, 9.67 ± 2.15 × 10 [p/sec/cm/sr]/[μW/cm]) with high-contrast ratios (5.91 ± 0.60, 2.80 ± 0.51). Additionally, experiments showed that the probe AmBF-QS-1 effectively guided tumor localization for precise resection and pathological examination. Collectively, the results demonstrate the potential of [F]AmBF-QS-1 as a promising dual-modality probe for noninvasive whole-body PET imaging to localize TNBC tumor as well as for NIRF imaging guidance to delineate tumor margins during surgical procedures.
三阴性乳腺癌（TNBC）是一种严重的恶性肿瘤，其特征是缺乏明确的生物标志物。研究表明，神经纤毛蛋白-1（NRP-1）在乳腺癌中高度过表达，其表达水平与肿瘤的发生、发展和预后密切相关，从而使NRP-1成为乳腺癌诊断和治疗的一个有前景的靶点，尤其是对于TNBC。在此，NRP-1被用作分子标记物，设计并合成了一种PET/NIRF双模态分子探针[F]AmBF-QS-1，用于TNBC的肿瘤定位和手术导航。非放射性NIRF探针AmBF-QS-1通过点击反应合成（化学纯度>95%），放射性探针[F]AmBF-QS-1通过一步法F标记法合成（放射化学纯度>95%，放射化学产率>15%）。对不同NRP-1表达水平的癌细胞进行荧光成像、流式细胞术和细胞摄取研究，以验证探针的特异性。MDA-MB-231异种移植瘤的PET和NIRF成像显示，[F]AmBF-QS-1对肿瘤摄取具有优异的特异性（8.41±0.86%ID/mL，9.67±2.15×10 [p/sec/cm/sr]/[μW/cm]），对比度高（5.91±0.60，2.80±0.51）。此外，实验表明，探针AmBF-QS-1有效地引导肿瘤定位以进行精确切除和病理检查。总体而言，结果表明[F]AmBF-QS-1作为一种有前景的双模态探针，具有用于非侵入性全身PET成像以定位TNBC肿瘤以及用于NIRF成像引导以在手术过程中描绘肿瘤边缘的潜力。
