2. Academic Validation
  3. Preclinical Evaluation of a Trop2-Targeted Peptide Probe for PET Imaging of Triple-Negative Breast Cancer

Preclinical Evaluation of a Trop2-Targeted Peptide Probe for PET Imaging of Triple-Negative Breast Cancer

  • Anal Chem. 2025 Oct 28;97(42):23598-23608. doi: 10.1021/acs.analchem.5c05242.
Yuan Zha 1 2 3,  Xue Zhu 1 2,  Yan Xue 1 2,  Zhihong Huang 1 2,  Shuang Wang 1 2,  Yang Jiao 1 2,  Yu Chen 4,  Ying Yao 3,  Ke Wang 1 2,  Jing Fang 1 2
Affiliations

Affiliations

  • 1 National Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
  • 2 Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
  • 3 Department of Pharmacy, Affiliated Women's Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu 214002, China.
  • 4 Affiliated Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu 214002, China.
PMID: 41105928 DOI: 10.1021/acs.analchem.5c05242
Abstract

Trophoblast cell surface antigen 2 (TROP2) has been extensively characterized as a clinically relevant pan-cancer biomarker that is overexpressed in multiple malignancies, including triple-negative breast Cancer (TNBC). In this study, we employed computational simulation strategies to develop peptide WP8 derived from midkine (MDK), a particular ligand of TROP2, and designed a Trop2-targeting radiotracer [68Ga]Ga-NOTA-PEG2-WP8 for positron emission tomography (PET) imaging of TROP2 expression. This radiotracer exhibits nanomolar affinity for TROP2, along with favorable stability and pharmacokinetic properties. Dynamic PET imaging revealed that [68Ga]Ga-NOTA-PEG2-WP8 displays significant and specific uptake in Trop2-positive TNBC tissues, enabling rapid and precise identification of TROP2 expression. Notably, this radiotracer demonstrated high sensitivity in detecting the response of TNBC tumor to Trop2-targeting antibody-drug conjugates (ADCs). Collectively, these findings indicate that the peptide-based radiotracer [68Ga]Ga-NOTA-PEG2-WP8 holds considerable potential as a noninvasive tool for accurately monitoring of TROP2 expression before, during, and after ADC-based therapies.

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