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Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Xia Li[1,2,3] ; Liu Yang[1,2,4] ; Cai Ping[1,2,3] ; Feng Yue[1,2,4] ; Yuan Hongmei[1,2,3] ; Tang Sufan[1,2,3] ; Wang Yin Wen[1,2,3] ; Liu Nan[1,5] ; Chen Yue[1,2,4] ; Zhou Zhijun[1,2,3,4] ;
机构： [1]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Jiangyang District, Luzhou, Sichuan, China. [3]Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [4]Institute of Nuclear Medicine, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [5]Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan, Chengdu, China
出处：
DOI： 10.1007/s11307-023-01804-x
ISSN：

关键词： Prostate-specific membrane antigen Halogen Radiopharmaceutical Prostate cancer Positron emission tomography

摘要：
Investigate the impact of various halogens on pharmacokinetics, biodistribution, and micro positron emission tomography/computed tomography (PET/CT) imaging of Glu-urea-Lys-based prostate-specific membrane antigen (PSMA) inhibitors.Based on the modification of SC691, a small molecule inhibitor of PSMA previously developed by our group, we synthesized 68Ga-labeled compounds by modifying the lysine terminal amino with different halogenated phenyl substituents. After complete characterization, in vitro and in vivo properties were studied.The [68Ga]Ga-DOTA-SC691-R possesses a high radiochemical yield (98-99%). The internalization values of [68Ga]Ga-DOTA-SC691-H, [68Ga]Ga-DOTA-SC691-Cl, and [68Ga]Ga-DOTA-SC691-Br in LNCaP cells all displayed time-dependent pattern enhanced with time. The results of in vitro competitive inhibition assay showed that the affinity of natGa-DOTA-SC691-R for PSMA had a trend of H < F < Cl < Br < I. The blocking imaging and dynamic imaging on micro-PET/CT of male non-obese diabetic/severe combined immunodeficiency mice with LNCaP tumors showed the rapid tumor targeting properties of [68Ga]Ga-DOTA-SC691-R with specificity for PSMA. Static imaging of micro-PEC/CT of these compounds could rapidly localize LNCaP tumors with decent image quality (except for [68Ga]Ga-DOTA-SC691-H). Biodistribution data showed that [68Ga]Ga-DOTA-SC691-R were metabolized via the kidney and tumor accumulation followed the order of H ≈ F ≈ Cl < I < Br uptake values at 1 h. [68Ga]Ga-DOTA-SC691-Br showed the highest tumor accumulation and retention (15.21 ± 5.57%ID/g at 30 min, 20.39 ± 4.38%ID/g at 60 min, and 13.30 ± 4.39%ID/g at 120 min), which is consistent with the results of the competitive inhibition assay and cell binding assay.It was demonstrated that the halogen substituent on the lysine terminal amino group on the Glu-urea-Lys backbone did positively affect the binding of [68Ga]Ga-DOTA-SC691-R to PSMA. The bulkier and less electronegative Br (or I) elements are preferred for structural modifications here.© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.

基金：
National Natural Science Foundation of China for funding this work (U20A20384), the Sichuan Science and Technology Foundation (2021YJ0131), the Doctoral Research Initiation Fund of Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province (HYX19001), and the Luzhou-Southwest Medical University Cooperative Application Foundation (2020LZXNYDJ50).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 4 区 医学
小类 | 4 区 核医学
最新[2023]版：
大类 | 4 区 医学
小类 | 4 区 核医学
JCR分区：
出版当年[2023]版：
Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
最新[2023]版：
Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Jiangyang District, Luzhou, Sichuan, China. [3]Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China.
通讯作者：
通讯机构： [1]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Jiangyang District, Luzhou, Sichuan, China. [3]Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [4]Institute of Nuclear Medicine, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China. [5]Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan, Chengdu, China
推荐引用方式(GB/T 7714)：
Xia Li,Liu Yang,Cai Ping,et al.Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties[J].MOLECULAR IMAGING AND BIOLOGY.2023,25(4):765-775.doi:10.1007/s11307-023-01804-x.
APA：
Xia Li,Liu Yang,Cai Ping,Feng Yue,Yuan Hongmei...&Zhou Zhijun.(2023).Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties.MOLECULAR IMAGING AND BIOLOGY,25,(4)
MLA：
Xia Li,et al."Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties".MOLECULAR IMAGING AND BIOLOGY 25..4(2023):765-775

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