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
Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Acta Pharm Sin B. 2022 Mar;12(3):1363-1376. doi: 10.1016/j.apsb.2021.09.016. Epub 2021 Sep 22.
Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the 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 [Cu]DPA and investigated the tumor engagement of [Cu/Ga]DPA in mouse models. Our results revealed that intact [Cu/Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.
由右旋（d）-氨基酸组成的肽作为一种潜在的治疗类别越来越受到关注。然而，我们对d-肽命运的了解有限。这凸显了对d-肽进行全身定量追踪以更好地理解它们与活体相互作用方式的必要性。在此，我们使用小鼠模型，通过正电子发射断层扫描（PET）追踪一种靶向程序性死亡配体1（PD-L1）的d-十二肽拮抗剂（DPA）的运动。更具体地说，我们剖析了[Cu]DPA的代谢途径，并研究了[Cu/Ga]DPA在小鼠模型中的肿瘤靶向情况。我们的结果显示，完整的[Cu/Ga]DPA主要通过肾脏清除，并在肿瘤中显著蓄积。此外，单剂量的[Cu]DPA有效延缓了肿瘤生长并提高了小鼠的存活率。总体而言，这些结果不仅加深了我们对d-肽命运的认识，也强调了d-肽作为放射性药物的实用性。
