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

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.
KEY WORDS D-peptide; PET imaging; Radiotheranostics; In vivo fate; PD-L1
Abbreviations: 2D, two-dimensional; 3D, three-dimensional; CPM, radioactivity per minute; DAB,
3,3-diaminobenzidine; DMEM, Dulbecco’s modified Eagle medium; DMSO, dimethyl sulfoxide;
DMF, dimethylformamide; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; DPA,
D-dodecapeptide antagonist; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; HCT,
hematocrit; H&E, Hematoxylin and Eosin; HPLC, high performance liquid chromatography; mAb,
monoclonal antibody; MD, molecular dynamics; MIP, maximum intensity projection; MIPD,
mirror-image phage display; PCNA, proliferating cell nuclear antigen; PD-L1, programmed deathligand 1; PET, positron emission tomography; PLC, platelet; RBC, red blood cells; TAC, time‒
activity curves; TFA, trifluoroacetic acid; TLC, thin layer chromatography; TRT, targeted
radionuclide therapy; WBC, white blood cell.

書誌情報

Acta Pharmaceutica Sinica B

巻 12, 号 3, p. 1363-1376, 発行日 2021-11

出版者

Chinese Academy of Medical Sciences

ISSN

収録物識別子タイプ

ISSN

収録物識別子

2211-3835

DOI

識別子タイプ

DOI

Versions

Ver.1

2023-05-15 16:53:45.498805

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Cite as

Kuan, Hu, Wu, Wenyu, Lin, Xie, Geng, Hao, Zhang, Yiding, Masayuki, Hanyu, Zhang, Lulu, Liu, Yinghuan, Kotaro, Nagatsu, Hisashi, Suzuki, Guo, Jialin, Wu, Yundong, Li, Zigang, Wang, Feng, Zhang, Ming-Rong, Kuan, Hu, Lin, Xie, Zhang, Yiding, Masayuki, Hanyu, Kotaro, Nagatsu, Hisashi, Suzuki, Zhang, Ming-Rong, n.d., Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors: Chinese Academy of Medical Sciences, 1363–1376 p.

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