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

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...

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Detalles Bibliográficos
Autores principales: Hu, Kuan, Wu, Wenyu, Xie, Lin, Geng, Hao, Zhang, Yiding, Hanyu, Masayuki, Zhang, Lulu, Liu, Yinghuan, Nagatsu, Kotaro, Suzuki, Hisashi, Guo, Jialin, Wu, Yundong, Li, Zigang, Wang, Feng, Zhang, Mingrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069398/
https://www.ncbi.nlm.nih.gov/pubmed/35530129
http://dx.doi.org/10.1016/j.apsb.2021.09.016
Descripción
Sumario: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 [(64)Cu]DPA and investigated the tumor engagement of [(64)Cu/(68)Ga]DPA in mouse models. Our results revealed that intact [(64)Cu/(68)Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [(64)Cu]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.