机构：[1]Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.[3]Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.[4]Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.[5]Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.[6]Department of Nuclear Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in various malignant tumors and has emerged as a promising target for tumor imaging. Bicyclic peptides, known for their conformational rigidity, metabolic stability, and membrane permeability, are ideal tracers for positron emission tomography (PET) imaging. In this study, we evaluated the feasibility of visualizing Nectin-4-positive tumors using radiolabeled bicyclic peptide derivatives and optimized the pharmacokinetics of radiotracers by introducing PEG chains of different lengths. Five PEGylated radiotracers radiolabeled with 68Ga3+ exhibited high radiochemical purity and stability. As the chain length increased, the Log D values decreased from -2.32 ± 0.13 to -2.50 ± 0.16, indicating a gradual increase in the hydrophilicity of the radiotracers. In vitro cell-binding assay results showed that the PEGylated bicyclic peptide exhibits nanomolar affinity, and blocking experiments confirmed the specific binding of the tracers to the Nectin-4 receptor. In vivo PET imaging and biodistribution studies in SW780 and 5637 xenograft mice showed that [68Ga]Ga-NOTA-PEG12-BP demonstrated optimal pharmacokinetics, characterized by rapid and good tumor uptake, faster background clearance, and improved tumor-to-tissue contrast. Finally, compared with 18F-FDG, PET imaging, in vivo blocking assays of [68Ga]Ga-NOTA-PEG12-BP and histological staining confirmed that specific tumor uptake was mediated by Nectin-4 receptors. The results indicated that [68Ga]Ga-NOTA-PEG12-BP was a promising PET radiotracer for Nectin-4 targeting, with applications for clinical translation.
基金：
This work was supported by the National Natural Science
Foundation of China (No. 81701740), the Luzhou-Southwest
Medical University Cooperative Application Foundation
(2020LZXNYDJ50), and the Science and Technology Project
of Sichuan Province (2024NSFSC0666).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
最新[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
JCR分区：
出版当年[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者机构：[1]Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Jiangyang District, Luzhou 646000, Sichuan, China.
推荐引用方式(GB/T 7714)：
Wan Qiang,Yuan Hongmei,Cai Ping,et al.Effects of PEGylation on Imaging Contrast of 68Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4[J].Molecular Pharmaceutics.2024,doi:10.1021/acs.molpharmaceut.4c00366.
APA：
Wan Qiang,Yuan Hongmei,Cai Ping,Liu Yang,Yan Ting...&Liu Nan.(2024).Effects of PEGylation on Imaging Contrast of 68Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4.Molecular Pharmaceutics,,
MLA：
Wan Qiang,et al."Effects of PEGylation on Imaging Contrast of 68Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4".Molecular Pharmaceutics .(2024)
