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

Acta Pharmaceutica Sinica B (Mar 2022)

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

Affiliations

Kuan Hu: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Wenyu Wu: Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
Lin Xie: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Hao Geng: State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China
Yiding Zhang: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Masayuki Hanyu: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Lulu Zhang: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Yinghuan Liu: State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China
Kotaro Nagatsu: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Hisashi Suzuki: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
Jialin Guo: Rensselaer Polytechnic Institute, Troy, NY 12180, USA
Yundong Wu: State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518038, China; Corresponding authors. Tel./fax: +81 43 3823709 (Mingrong Zhang), +86 25 52271455 (Feng Wang), +86 755 26033616 (Zigang Li), +86 755 26611113 (Yundong Wu).
Zigang Li: State Key Laboratory of Chemical Oncogenomics, the School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China; Corresponding authors. Tel./fax: +81 43 3823709 (Mingrong Zhang), +86 25 52271455 (Feng Wang), +86 755 26033616 (Zigang Li), +86 755 26611113 (Yundong Wu).
Feng Wang: Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China; Corresponding authors. Tel./fax: +81 43 3823709 (Mingrong Zhang), +86 25 52271455 (Feng Wang), +86 755 26033616 (Zigang Li), +86 755 26611113 (Yundong Wu).
Mingrong Zhang: Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; Corresponding authors. Tel./fax: +81 43 3823709 (Mingrong Zhang), +86 25 52271455 (Feng Wang), +86 755 26033616 (Zigang Li), +86 755 26611113 (Yundong Wu).

Journal volume & issue: Vol. 12, no. 3
pp. 1363 – 1376

Abstract

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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.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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