TROP2-targeted NIR-II fluorescence imaging for visualizing surgical margins and metastatic sentinel lymph nodes in breast cancers

K Kang-Liang Lou (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) J Jing-Wen Bai (The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan) H Hong-Tan Liu (Ministry of Education Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University) L Lin-Ling Lin (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) C Cheng-Xi Li (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) Y Yi-Yang Gao (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) S Sheng-Jie Lin (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) Y Yi-Fei Pei (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) X Xiao-Long Wei (Department of Pathology, Cancer Hospital of Shantou University Medical College) Y Yi-Xin Chen (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) Y Yi-Yin Tang (The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan) H Hong-Yu Chen (Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University) Z Zhi-Yao Li (Department of Medical Ultrasound, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan) R Rong Guo S Shi-Cong Tang (The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan) C Chuan-Liu Wu (Ministry of Education Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University) G Guo-Jun Zhang (The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan)

Abstract

In early breast cancer surgery (EBC), free margins significantly decrease local recurrence in breast-conserving surgery (BCS), while metastatic status of sentinel lymph node (SLN) impacts axillary management. However, intraoperative visualization of margins and metastatic SLNs (mSLNs) remains challenging. Here, we report a second-window near-infrared (NIR-II) fluorescence probe by conjugating ICG to TROP2-targeting cyclic peptide (TTP-ICG). Our results showed that TTP-ICG specifically binds to TROP2-expressing cells in vitro and identifies TROP2-positive tumors in vivo. In addition, TTP-ICG enabled efficient intraoperative evaluation of surgical margins and visualization of mSLNs at a submillimeter level in preclinical models. Additionally, we optimized the rapid incubation imaging method (RIIM) by shortening the procedure to less than 8 min, illustrating TTP-ICG’s high performance in distinguishing malignant from normal tissues/fibroadenoma lesions as well as detecting metastatic lymph nodes in a cohort of 59 patients. Thus, this TROP2-targeting probe demonstrates its significance for fluorescence imaging-guided surgery with dual applicability in EBC, providing translational potential for further clinical decision-making.

Article Details

Volume / Issue Vol. 123, Issue 8
Published February 24, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (17)

K

Kang-Liang Lou

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

J

Jing-Wen Bai

The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan

H

Hong-Tan Liu

Ministry of Education Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University

L

Lin-Ling Lin

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

C

Cheng-Xi Li

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

Y

Yi-Yang Gao

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

S

Sheng-Jie Lin

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

Y

Yi-Fei Pei

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

X

Xiao-Long Wei

Department of Pathology, Cancer Hospital of Shantou University Medical College

Y

Yi-Xin Chen

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

Y

Yi-Yin Tang

The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan

H

Hong-Yu Chen

Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer and Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, School of Medicine, Xiamen University

Z

Zhi-Yao Li

Department of Medical Ultrasound, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan

R

Rong Guo

S

Shi-Cong Tang

The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan

C

Chuan-Liu Wu

Ministry of Education Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University

G

Guo-Jun Zhang

The Breast Center and the Cancer Institute of Yunnan Cancer Hospital, Yunnan Key Laboratory of Molecular Imaging in Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan