Original articles
Kuan Hu, Wenyu Wu, Lin Xie, Hao Geng, Yiding Zhang, Masayuki Hanyu, Lulu Zhang, Yinghuan Liu, Kotaro Nagatsu, Hisashi Suzuki, Jialin Guo, Yundong Wu, Zigang Li, Feng Wang, Mingrong Zhang. Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors[J]. Acta Pharmaceutica Sinica B, 2022, 12(3): 1363-1376

Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors
Kuan Hua, Wenyu Wub, Lin Xiea, Hao Gengc, Yiding Zhanga, Masayuki Hanyua, Lulu Zhanga, Yinghuan Liuc, Kotaro Nagatsua, Hisashi Suzukia, Jialin Guof, Yundong Wuc,e, Zigang Lic,d, Feng Wangb, Mingrong Zhanga
a. Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan;
b. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China;
c. State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China;
d. Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China;
e. Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518038, China;
f. Rensselaer Polytechnic Institute, Troy, NY 12180, USA
Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of[64Cu]DPA and investigated the tumor engagement of[64Cu/68Ga]DPA in mouse models. Our results revealed that intact[64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of[64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.
Key words:    d-peptide    PET imaging    Radiotheranostics    In vivo fate    PD-L1   
Received: 2021-07-13     Revised: 2021-09-02
DOI: 10.1016/j.apsb.2021.09.016
Funds: We thank the staff of the National Institutes for Quantum and Radiological Sciences and Technology (QST) for their support in cyclotron operation, radioisotope production, radiosynthesis, and animal experiments. We sincerely thank the financial support from the JSPS KAKENHI grant Nos. 19K17156, 21H02873, 21K07659, and 20H03635, Japan. This research is also supported by QST President's Strategic Grant (Exploratory Research, Japan). We also thank the financial support from the National Natural Science Foundation of China (82003532), General Project of Science and Technology Development Fund of Nanjing Medical University (NMUB2019154, China), the second round of Nanjing Clinical Medical Center "Nanjing Nuclear Medicine Center", and the China Postdoctoral Science Foundation (2019M650302).
Corresponding author: Yundong Wu,E-mai:wuyd@pkusz.edu.cn;Zigang Li,E-mai:lizg@pkusz.edu.cn;Feng Wang,E-mai:fengwangcn@hotmail.com;Mingrong Zhang,E-mai:zhang.ming-rong@qst.go.jp     Email:wuyd@pkusz.edu.cn;lizg@pkusz.edu.cn;fengwangcn@hotmail.com;zhang.ming-rong@qst.go.jp
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Kuan Hu
Wenyu Wu
Lin Xie
Hao Geng
Yiding Zhang
Masayuki Hanyu
Lulu Zhang
Yinghuan Liu
Kotaro Nagatsu
Hisashi Suzuki
Jialin Guo
Yundong Wu
Zigang Li
Feng Wang
Mingrong Zhang

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