Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors.

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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Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors.

Author: Kuan HU ¹ ; Wenyu WU ² ; Lin XIE ¹ ; Hao GENG ³ ; Yiding ZHANG ¹ ; Masayuki HANYU ¹ ; Lulu ZHANG ¹ ; Yinghuan LIU ³ ; Kotaro NAGATSU ¹ ; Hisashi SUZUKI ¹ ; Jialin GUO ⁴ ; Yundong WU ³ ; Zigang LI ³ ; Feng WANG ² ; Mingrong ZHANG ¹
Author Information

1. Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
2. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
3. State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China.
4. Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Publication Type:Journal Article
Keywords: In vivo fate; PD-L1; PET imaging; Radiotheranostics; d-peptide
From: Acta Pharmaceutica Sinica B 2022;12(3):1363-1376
CountryChina
Language:English
Abstract: 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.