@article{oai:repo.qst.go.jp:00085188,
 author = {Kuan, Hu and Wu, Wenyu and Lin, Xie and Geng, Hao and Zhang, Yiding and Masayuki, Hanyu and Zhang, Lulu and Liu, Yinghuan and Kotaro, Nagatsu and Hisashi, Suzuki and Guo, Jialin and Wu, Yundong and Li, Zigang and Wang, Feng and Zhang, Ming-Rong and Kuan, Hu and Lin, Xie and Zhang, Yiding and Masayuki, Hanyu and Kotaro, Nagatsu and Hisashi, Suzuki and Zhang, Ming-Rong},
 issue = {3},
 journal = {Acta Pharmaceutica Sinica B},
 month = {Nov},
 note = {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.},
 pages = {1363--1376},
 title = {Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors},
 volume = {12},
 year = {2021}
}