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A CTSC-activated visible-to-NIR probe series and a PEGylated NIR probe (YF-2) further support robust detection, including lung-metastatic 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metastasis-related biomarker  \nShan Zuo1, Yanhua Li1, Yushi Chen2, Gangwei Jiang1*, Zhixuan Zhou1, Tian-Bing Ren1, Lanlan Chen2, Sulai Liu3, Shulin Huang4*, Xiao-Bing Zhang1, Lin Yuan1*  \nAccurate differentiation of benign and malignant breast tumors is paramount for establishing schemes of breast cancer treatment and prognosis. Here we report a near-infrared (NIR) fluorescence probe (YF-1) with the overexpressed cathepsin C (CTSC) in metastatic breast tumors as the detecting substrate. This probe allows accurate identification of malignant tumor tissue specimens among tumor tissue specimens with unknown properties in a blind study. Importantly, a series of visible to NIR CTSC-activated fluorescence probes based on the same strategy realize effective identification of malignant tumor tissues, suggesting that CTSC could be the specific identification substrate of malignant breast tumors. Furthermore, a hydrophilic PEG moiety is coupled into YF-1, producing another CTSC-activated NIR probe (YF-2). YF-2 has excellent tumor-targeting capability, enabling the visualization of lung-metastatic breast tumors. The excellent detection accuracy and construction versatility of CTSC probes pave the way for preoperative diagnosis of malignant breast tumors.  \ncopyright © 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) .  \nINTRODUCTION  \nTumors are serious threats to human health and have become the leading cause of mortality (1, 2) . In various types of tumors, breast tumors are at the forefront of morbidity and mortality among females (3) . Breast tumors can be classified into benign and malignant tumors based on the phenotypic appearance, tumor size, and stage. Generally, benign breast tumors grow slowly and have clear boundaries and regular morphology. Malignant breast tumors display the rapid rate of growth and phenotypic appearance over benign breast tumors and have a lot of pseudopods to erode the normal glands, which endow it with a high metastatic potential (4) . Notably, more than 90% of breast cancer mortalities are caused by metastasis (5–7) . Clinically, the breast tumors enlarge rapidly over a short period due to the transformation of tumor’s characteristics from benign into malignant (8). Therefore, identification of the tumor’s characteristic (benign/malignancy) is of great concern for the early and accurate diagnosis of breast tumors (9, 10) .  \nUntil now, some medical imaging techniques have been applied for the diagnosis of breast cancers, including magnetic resonance imaging, positron emission tomography, x-ray computed tomography, ultrasound, and so on (11–13) . These techniques can visualize the location and size of tumors but are difficult to provide tumor’s characteristic. The clinical diagnosis of malignant breast tumors mainly relies on the needle biopsy, which is a time-consuming and painful process (14–16). Moreover, needle biopsy could induce implant metastasis and cannot map the metastasis extent of malignant  \n1State Key laboratory of chemo and Biosensing, college of chemistry and chemical engineering, hunan University, changsha, 410082, china. 2MOe Key laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key laboratory of Analysis and detection technology for Food Safety, college of chemistry, Fuzhou University, Fuzhou, 350108, china. 3department of hepatobiliary Surgery/central laboratory, hunan Provincial People’s hospital (the First Affiliated hospital of hunan normal University), changsha, 410005, china. 4department of Breast and thyroid Surgery, hunan Provincial People’s hospital (the First Affiliated hospital of hunan normal University), changsha, 410005, china.  \n*correspondin","cbCaiezZBPRBuI1z","https://ap.wps.com/l/cbCaiezZBPRBuI1z","pdf",2926852,12,"English","# Introduction\n## Imaging and diagnostic needs\n## Fluorescence probe–based imaging\n## Role of cathepsin C (CTSC) in metastasis","[{\"question\":\"What is the main goal of the reported method for malignant breast tumors?\",\"answer\":\"To accurately differentiate malignant from benign breast tumor tissue and support early diagnosis and prognosis-related assessment using imaging.\"},{\"question\":\"How does the YF-1 fluorescence probe work?\",\"answer\":\"YF-1 is a near-infrared fluorescence probe that uses CTSC overexpression in metastatic breast tumors as the detecting substrate, enabling identification of malignant specimens in blind study conditions.\"},{\"question\":\"Why is CTSC emphasized in this study?\",\"answer\":\"CTSC is confirmed to be strongly associated with breast cancer metastasis to the lung, with clinical evidence linking higher CTSC activity to increased brain/lung metastases and lower patient survival.\"}]","Rapid sorting and auxiliary evaluation of malignant breast tumors by accurate imaging analysis of metastasis-related biomarker | PDF",1790191927]