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

• Main Authors: Kuan Hu (Author), Wenyu Wu (Author), Lin Xie (Author), Hao Geng (Author), Yiding Zhang (Author), Masayuki Hanyu (Author), Lulu Zhang (Author), Yinghuan Liu (Author), Kotaro Nagatsu (Author), Hisashi Suzuki (Author), Jialin Guo (Author), Yundong Wu (Author), Zigang Li (Author), Feng Wang (Author), Mingrong Zhang (Author)
• Format: Book
• Published: Elsevier, 2022-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2211-3835
10.1016/j.apsb.2021.09.016