A GRPR Antagonist Peptide-Based Pretargeting Strategy Overcoming Molecule Internalization for Enhanced Tumor Imaging.
4 affiliations
- 1Department of Radiology, The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
- 2Institute of Biomedical Engineering, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.
- 3Biomedical Basic Research Center (BBRC) of Jiangsu Province, Soochow University, Suzhou, Jiangsu 215123, China.
- 4The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Abstract
Pretargeting is an emerging strategy for tumor imaging that offers improved specificity and reduced off-target toxicity compared to conventional direct targeting approaches. However, a major limitation lies in the rapid internalization of pretargeting molecules, which reduces the availability of binding sites for effector probes and compromises imaging performance. In this study, we present a GRPR-targeted pretargeting system designed to overcome this challenge by employing the GRPR antagonist peptide RM26, which remains on the cell surface after receptor binding and thus minimizes internalization. The system is based on a bioorthogonal inverse electron-demand Diels-Alder reaction between IBA-RM26-TCO and 99mTc-HYNIC-Tz, which is completed quantitatively within 10 min under physiological conditions, with excellent stability, as evidenced by over 93% radiochemical purity after 24 h. In vitro experiments confirmed that RM26 maintained high GRPR binding affinity with minimal internalization, facilitating robust bioorthogonal reactivity. In vivo SPECT/CT imaging in GRPR-positive U-87MG xenograft mice further demonstrated more than 2-fold higher tumor uptake and an improved tumor-to-muscle ratio compared to direct targeting. Collectively, this work establishes a GRPR antagonist peptide-based pretargeting platform that not only addresses the internalization barrier but also enhances diagnostic performance, offering a safer and more effective approach for precision tumor imaging.
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BibTeX
@article{sun2026grpr,
title = {{A GRPR Antagonist Peptide-Based Pretargeting Strategy Overcoming Molecule Internalization for Enhanced Tumor Imaging.}},
author = {Chaoping Sun and Xiuqi Hu and Zhongsheng Zhao and Yun Gao and Mengdan Xu and Ning Wang and Qianqian Zhang and Lishu Zhao and Jianxian Ge and Jianfeng Zeng},
journal = {Chemical \& biomedical imaging},
year = {2026},
month = jun,
doi = {10.1021/cbmi.6c00069},
url = {https://europepmc.org/article/MED/42953307},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A GRPR Antagonist Peptide-Based Pretargeting Strategy Overcoming Molecule Internalization for Enhanced Tumor Imaging.
AU - Chaoping Sun
AU - Xiuqi Hu
AU - Zhongsheng Zhao
AU - Yun Gao
AU - Mengdan Xu
AU - Ning Wang
AU - Qianqian Zhang
AU - Lishu Zhao
AU - Jianxian Ge
AU - Jianfeng Zeng
PY - 2026
DA - 2026/06/08
JO - Chemical & biomedical imaging
DO - 10.1021/cbmi.6c00069
UR - https://europepmc.org/article/MED/42953307
AB - Pretargeting is an emerging strategy for tumor imaging that offers improved specificity and reduced off-target toxicity compared to conventional direct targeting approaches. However, a major limitation lies in the rapid internalization of pretargeting molecules, which reduces the availability of binding sites for effector probes and compromises imaging performance. In this study, we present a GRPR-targeted pretargeting system designed to overcome this challenge by employing the GRPR antagonist peptide RM26, which remains on the cell surface after receptor binding and thus minimizes internalization. The system is based on a bioorthogonal inverse electron-demand Diels-Alder reaction between IBA-RM26-TCO and 99mTc-HYNIC-Tz, which is completed quantitatively within 10 min under physiological conditions, with excellent stability, as evidenced by over 93% radiochemical purity after 24 h. In vitro experiments confirmed that RM26 maintained high GRPR binding affinity with minimal internalization, facilitating robust bioorthogonal reactivity. In vivo SPECT/CT imaging in GRPR-positive U-87MG xenograft mice further demonstrated more than 2-fold higher tumor uptake and an improved tumor-to-muscle ratio compared to direct targeting. Collectively, this work establishes a GRPR antagonist peptide-based pretargeting platform that not only addresses the internalization barrier but also enhances diagnostic performance, offering a safer and more effective approach for precision tumor imaging.
SN - 2832-3637
ER -