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However, our understanding of the in vivo fate of D-peptides\nis limited. This highlights the need for whole-body, quantitative tracking of D-peptides to better\nunderstand how they interact with the living body. Here, we used mouse models to track the\nmovement of a programmed death-ligand 1 (PD-L1)-targeting D-dodecapeptide antagonist (DPA)\nusing positron emission tomography (PET). More specifically, we profiled the metabolic routes of\n[\n64Cu]DPA and investigated the tumor engagement of [\n64Cu/68Ga]DPA in mouse models. Our results\nrevealed that intact [\n64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable\naccumulation in tumors. Moreover, a single dose of [\n64Cu]DPA effectively delayed tumor growth\nand improved the survival of mice. Collectively, these results not only deepen our knowledge of the\nin vivo fate of D-peptides, but also underscore the utility of D-peptides as radiopharmaceuticals.\nKEY WORDS D-peptide; PET imaging; Radiotheranostics; In vivo fate; PD-L1\nAbbreviations: 2D, two-dimensional; 3D, three-dimensional; CPM, radioactivity per minute; DAB,\n3,3-diaminobenzidine; DMEM, Dulbecco’s modified Eagle medium; DMSO, dimethyl sulfoxide;\nDMF, dimethylformamide; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; DPA,\nD-dodecapeptide antagonist; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; HCT,\nhematocrit; H\u0026E, Hematoxylin and Eosin; HPLC, high performance liquid chromatography; mAb,\nmonoclonal antibody; MD, molecular dynamics; MIP, maximum intensity projection; MIPD,\nmirror-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‒\nactivity curves; 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Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors
https://repo.qst.go.jp/records/85188
https://repo.qst.go.jp/records/85188594e7bc0-00ba-47c5-8693-fb4159364732
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-10-08 | |||||
タイトル | ||||||
タイトル | Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Kuan, Hu
× 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 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. |
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書誌情報 |
Acta Pharmaceutica Sinica B 巻 12, 号 3, p. 1363-1376, 発行日 2021-11 |
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出版者 | ||||||
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 | |||||
関連識別子 | 10.1016/j.apsb.2021.09.016 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.sciencedirect.com/science/article/pii/S2211383521003580?via%3Dihub |