机构：[1]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000 Sichuan, China[3]Institute of Nuclear Medicine and Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou 646000 Sichuan, China[4]Institute of Nuclear Medicine, Southwest Medical University, Luzhou 646000 Sichuan, China[5]Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China四川省人民医院
Since prostate-specific membrane antigen (PSMA) is upregulated in nearly all stages of prostate cancer (PCa), PSMA can be considered a viable diagnostic biomarker and treatment target in PCa. In this study, we have developed five 68Ga-labeled PSMA-targeted tracers, 68Ga-Flu-1, 68Ga-Flu-2, 68Ga-9-Ant, 68Ga-1-Nal, and 68Ga-1-Noi, to investigate the effect of lipophilic bulky groups on the pharmacokinetics of PSMA inhibitors compared to 68Ga-PSMA-11 and then explore their in vitro and in vivo properties. 68Ga-labeled PSMA inhibitors were obtained in 88.53-99.98% radiochemical purity and at the highest specific activity of up to 20 MBq/μg. These compounds revealed a highly efficient uptake and internalization into LNCaP cells and increased over time. PET imaging and biodistribution studies were performed in mice bearing PSMA expressing LNCaP prostate cancer xenografts. All tracers enabled clear visualization of tumors in PET images with excellent tumor-to-background contrast. The biodistribution studies showed that all these radioligands were excreted mainly via the renal pathway. The in vivo biodistribution of 68Ga-Flu-1 revealed higher tumor uptake (40.11 ± 9.24 %ID/g at 2 h p.i.) compared to 68Ga-PSMA-11 (28.10 ± 5.96 %ID/g at 2 h p.i.). Both in vitro and in vivo experiments showed that chemical modification of the lysine fragment significantly impacts tumor-targeting and pharmacokinetic properties. Great potential to serve as new PET tracers for prostate cancer has been revealed with these radiotracers─68Ga-Flu-1 in particular.
基金：
National Natural Science
Foundation of China for funding this work (U20A20384), 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 Sichuan Science and Technology
Foundation (2021YJ0131).
语种：
外文
被引次数：
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, Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000 Sichuan, China[3]Institute of Nuclear Medicine and Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou 646000 Sichuan, China
通讯作者：
通讯机构：[1]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China[2]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000 Sichuan, China[3]Institute of Nuclear Medicine and Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou 646000 Sichuan, China[4]Institute of Nuclear Medicine, Southwest Medical University, Luzhou 646000 Sichuan, China[5]Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China[*1]Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China[*2]Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000 Sichuan, China[*3]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000 Sichuan, China[*4]Institute of Nuclear Medicine, Southwest Medical University, Luzhou 646000 Sichuan, China[*5]Institute of Nuclear Medicine and Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou 646000 Sichuan, China
推荐引用方式(GB/T 7714)：
Cai Ping,Tang Sufan,Xia Li,et al.Improve the Biodistribution with Bulky and Lipophilic Modification Strategies on Lys-Urea-Glu-Based PSMA-Targeting Radiotracers[J].MOLECULAR PHARMACEUTICS.2023,doi:10.1021/acs.molpharmaceut.2c01101.
APA：
Cai Ping,Tang Sufan,Xia Li,Wang Yinwen,Liu Yang...&Zhou Zhijun.(2023).Improve the Biodistribution with Bulky and Lipophilic Modification Strategies on Lys-Urea-Glu-Based PSMA-Targeting Radiotracers.MOLECULAR PHARMACEUTICS,,
MLA：
Cai Ping,et al."Improve the Biodistribution with Bulky and Lipophilic Modification Strategies on Lys-Urea-Glu-Based PSMA-Targeting Radiotracers".MOLECULAR PHARMACEUTICS .(2023)
