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PSMA 适体基双功能 PET 和荧光探针的临床前评价。

Preclinical Evaluation of a PSMA Aptamer-Based Bifunctional PET and Fluorescent Probe.

机构信息

School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.

出版信息

Bioconjug Chem. 2024 Sep 18;35(9):1352-1362. doi: 10.1021/acs.bioconjchem.4c00292. Epub 2024 Aug 26.

DOI:10.1021/acs.bioconjchem.4c00292
PMID:39187748
Abstract

Prostate cancer is the most prevalent malignant tumor affecting male individuals worldwide. The accurate early detection of prostate cancer is crucial to preventing unnecessary diagnosis and subsequent excessive treatment. Prostate-specific membrane antigen (PSMA) has emerged as a promising biomarker for the diagnosis of prostate cancer. In this study, a dual-modality imaging probe utilizing aptamer technology was developed for positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging, and the specificity and sensitivity of the probe toward PSMA were evaluated both in vitro and in vivo. The probe precursor was synthesized via automated solid-phase oligonucleotide synthesis. Subsequently, the PET/NIRF dual-modality probe was successfully prepared and exhibited favorable fluorescence properties and stability in vitro. The binding specificity of to PSMA was assessed through flow cytometry, fluorescence imaging, and cellular uptake experiments in LNCaP cells and PC-3 cells. In vivo PET/NIRF imaging studies demonstrated the sensitive and specific binding of to PSMA. Overall, the PET/NIRF dual-modality probe shows promise for the diagnosis of prostate cancer and for the fluorescence-guided identification of PSMA-positive cancer lesions during surgical procedures.

摘要

前列腺癌是全球男性中最常见的恶性肿瘤。准确早期检测前列腺癌对于预防不必要的诊断和随后的过度治疗至关重要。前列腺特异性膜抗原(PSMA)已成为诊断前列腺癌的有前途的生物标志物。在这项研究中,开发了一种利用适体技术的双模式成像探针,用于正电子发射断层扫描/近红外荧光(PET/NIRF)成像,并在体外和体内评估了探针对 PSMA 的特异性和敏感性。通过自动固相寡核苷酸合成合成了探针前体。随后,成功制备了 PET/NIRF 双模式探针,并在体外表现出良好的荧光性质和稳定性。通过流式细胞术、荧光成像和 LNCaP 细胞和 PC-3 细胞的细胞摄取实验评估了 与 PSMA 的结合特异性。体内 PET/NIRF 成像研究表明 与 PSMA 的敏感和特异性结合。总体而言,PET/NIRF 双模式探针 有望用于诊断前列腺癌,并在手术过程中荧光引导识别 PSMA 阳性癌病变。

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