Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2024-09-19 DOI:10.1021/acs.molpharmaceut.4c00799

Zuojie Li, Yuhao Jiang, Qing Ruan, Guangxing Yin, Peiwen Han, Xiaojiang Duan, Junbo Zhang

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引用次数: 0

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 ^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.

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针对 PSMA 的 99mTc 标记含 DPro-Gly 的示踪剂的合成与评估

前列腺特异性膜抗原（PSMA）的特异性表达使其成为诊断和治疗前列腺癌的理想靶点。目前，已开发出许多 99mTc 标记的 PSMA 靶向示踪剂。然而，这些 99mTc 标记的示踪剂在肾脏的高吸收率是限制其临床应用的一个常见问题。本研究以DPro-Gly为连接体合成了配体（EUKPG），并制备和评估了三种99m锝标记复合物（[99m锝]Tc-EUKPG-EDDA、[99m锝]Tc-EUKPG-TPPTS、[99m锝]Tc-EUKPG-TPPMS）与不同的连接体。其中，[99mTc]Tc-EUKPG-EDDA 显示出最有利的药代动力学特性，在肾脏的摄取量显著降低（14.04 ± 0.23% ID/g），清除迅速，在非靶器官的摄取量低，因此表现出较高的肿瘤-背景比（肿瘤/血液：7.47，肿瘤/肌肉：12.65）。亲和性研究表明，它在体内和体外对 PSMA 都具有高度特异性。因此，[99mTc]Tc-EUKPG-EDDA 作为靶向 PSMA 进行肿瘤成像的分子示踪剂具有很大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Pharmaceutics 医学-药学

CiteScore

8.00

自引率

6.10%

发文量

391

审稿时长

2 months

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.