Latest progress and prospect of NRP-1 targeted molecular probes for breast cancer diagnosis

doi:10.19401/j.cnki.1007-3639.2025.02.012

Abstract

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

CLC Number:

R737.9

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.

Figures/Tables 1

References 40

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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