NRP-1靶向分子探针助力乳腺癌诊断的最新进展及展望

doi:10.19401/j.cnki.1007-3639.2025.02.012

摘要/Abstract

摘要：

乳腺癌是全球女性最常见的恶性肿瘤，其中三阴性乳腺癌（triple-negative breast cancer，TNBC）具有高度侵袭性与转移性，近年其发病率逐步上升并呈年轻化趋势。随着对乳腺癌分子机制的深入研究，神经毡蛋白-1（neuropilin-1，NRP-1）作为一种跨膜蛋白，被证实与乳腺癌特别是TNBC的转移及患者预后密切相关，已经成为乳腺癌诊断和治疗的潜在靶点。利用核医学、光学及多模态等成像技术可以无创、实时、精准地检测NRP-1的表达和分布，对于乳腺癌的早期诊断、分期以及治疗和疗效监测具有重要的指导意义。核医学探针将放射性核素（如⁶⁸Ga、^99mTc等）与特定的靶向配体结合，从而特异性靶向肿瘤细胞或组织，并通过正电子发射体层成像（positron emission tomography，PET）或单光子发射计算机体层成像（single photon emission computed tomography，SPECT）实现对乳腺癌的灵敏特异性诊断。随着医学影像及各交叉学科的发展，靶向NRP-1的多模态分子探针[⁶⁸Ga]Ga-NODAGA-K(Cy5)DKPPR将PET的高灵敏度和近红外荧光（near-infrared fluorescence，NIRF）的高分辨率优势相结合，实现乳腺癌术前精确诊断并在术中提供实时荧光导航，有助于更准确地识别和切除肿瘤。本文对NRP-1靶向分子探针在乳腺癌诊断中的优缺点进行系统比较，并阐述各类探针在乳腺癌诊疗领域的适用范围及最新研究进展，以期为乳腺癌靶向分子探针的研发及临床应用提供参考。

关键词: 乳腺癌, 神经毡蛋白-1, 肿瘤诊断, 分子成像, 分子探针

Abstract:

Breast cancer is one of the most prevalent malignant tumor in women worldwide, in which, triple-negative breast cancer (TNBC) is highly invasive and metastatic. In recent years, the incidence rate of TNBC has gradually increased and shown a trend of younger age. With the in-depth research on the molecular mechanism of breast cancer, neuropilin-1 (NRP-1), a transmembrane protein, has been found to be associated with metastasis and prognosis of breast cancer, particularly TNBC. Therefore, NRP-1 has become a promising target for the diagnosis and treatment of breast cancer. The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine, optical imaging and multimodal imaging methods in a non-invasive, real-time and accurate manner, which has significant application value in the early diagnosis, staging, treatment, and prognosis evaluation of breast cancer. Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides (e.g., ⁶⁸Ga and ^99mTc) with specific molecular ligands, and the signal is captured using positron emission tomography (PET) or single-photon emission computed tomography (SPECT), allowing for sensitive diagnosis of breast cancer. With the development of medical imaging and other interdisciplinary subjects, the NRP-1 targeted multimodal molecular probe [⁶⁸Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence (NIRF) to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery, enhancing the accuracy of tumor tissue identification and excision. In this paper, the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared, and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described, in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.

Key words: Breast cancer, Neuropilin-1 (NRP-1), Tumor diagnosis, Molecular imaging, Molecular probes

中图分类号:

R737.9

蔡舒玥, 谢佺, 周雨萱, 刘清竹, 邱玲, 林建国. NRP-1靶向分子探针助力乳腺癌诊断的最新进展及展望[J]. 中国癌症杂志, 2025, 35(2): 249-254.

CAI Shuyue, XIE Quan, ZHOU Yuxuan, LIU Qingzhu, QIU Ling, LIN Jianguo. Latest progress and prospect of NRP-1 targeted molecular probes for breast cancer diagnosis[J]. China Oncology, 2025, 35(2): 249-254.

图/表 1

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Probes	Imaging mode	Advantages and disadvantages	Applicable scenarios
[⁶⁸Ga]Ga-NOTA-PEG_4-CK2^[22]	PET	High sensitivity and rapid metabolism, only be imaged within 1 h	Early diagnosis and treatment monitoring
⁶⁸Ga-DOTA-RGD-ATWLPPR^[30]	PET	Dual-target accurate imaging, fewer detection models	Early diagnosis and precise localization of tumors
^99mTc-CK3^[31]	SPECT	Prolonged imaging (at least 4 h), lower resolution	Tumor diagnosis and staging
[^99mTc]Tc-HYNIC-A7R /[^99mTc]Tc-HYNIC-^DA7R^[23]	SPECT	Rapid renal clearance, lower resolution	Tumor diagnosis and treatment monitoring
^99mTc-HYNIC-iRGD^[32]	SPECT	Dual-target accurate imaging, lower resolution	Tumor diagnosis and treatment monitoring
Cy5-CK3^[31]	NIRF	Prolonged imaging (at least 12 h), background interference	Image-guided surgery
QS-1/QS-2^[25]	NIRF	Prolonged imaging (at least 96 h), poorer tissue penetration	Image-guided surgery
RPP@TQTCD^[26]	NIRF	Targeting tumors with photothermal therapy, high non-target tissue uptake	Integration of diagnosis and treatment
FPPT@Axi^[33]	NIRF	Prolonged imaging (at least 24 h), combining photodynamic therapy	Integration of diagnosis and treatment
[⁶⁸Ga]Ga-NODAGA-K(Cy5)DKPPR^[29]	NIRF/PET	Comprehensive image information, complex preparation	PET for diagnosis and NIRF for guided surgery