{"title":"针对 PSMA 的 99mTc 标记含 DPro-Gly 的示踪剂的合成与评估","authors":"Zuojie Li, Yuhao Jiang, Qing Ruan, Guangxing Yin, Peiwen Han, Xiaojiang Duan, Junbo Zhang","doi":"10.1021/acs.molpharmaceut.4c00799","DOIUrl":null,"url":null,"abstract":"The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many <sup>99m</sup>Tc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these <sup>99m</sup>Tc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using <sub>D</sub>Pro-Gly as the linker was synthesized and three <sup>99m</sup>Tc-labeled complexes ([<sup>99m</sup>Tc]Tc-EUKPG-EDDA, [<sup>99m</sup>Tc]Tc-EUKPG-TPPTS, [<sup>99m</sup>Tc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both <i>in vivo</i> and <i>in vitro</i>. Therefore, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA\",\"authors\":\"Zuojie Li, Yuhao Jiang, Qing Ruan, Guangxing Yin, Peiwen Han, Xiaojiang Duan, Junbo Zhang\",\"doi\":\"10.1021/acs.molpharmaceut.4c00799\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many <sup>99m</sup>Tc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these <sup>99m</sup>Tc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using <sub>D</sub>Pro-Gly as the linker was synthesized and three <sup>99m</sup>Tc-labeled complexes ([<sup>99m</sup>Tc]Tc-EUKPG-EDDA, [<sup>99m</sup>Tc]Tc-EUKPG-TPPTS, [<sup>99m</sup>Tc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both <i>in vivo</i> and <i>in vitro</i>. Therefore, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.\",\"PeriodicalId\":52,\"journal\":{\"name\":\"Molecular Pharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.molpharmaceut.4c00799\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.molpharmaceut.4c00799","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA
The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.