基于 PSMA 适体的双功能 PET 和荧光探针的临床前评估。
Preclinical Evaluation of a PSMA Aptamer-Based Bifunctional PET and Fluorescent Probe.
发表日期:2024 Aug 26
作者:
Sudong Kong, Ying Peng, Qingzhu Liu, Quan Xie, Ling Qiu, Jianguo Lin, Minhao Xie
来源:
BIOCONJUGATE CHEMISTRY
摘要:
前列腺癌是影响全球男性个体的最常见的恶性肿瘤。前列腺癌的准确早期检测对于防止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景的生物标志物。在本研究中,开发了一种利用适体技术的双模态成像探针,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。探针前体 NOTA-PSMA-Cy5 通过自动固相寡核苷酸合成来合成。随后,成功制备了PET/NIRF双模态探针[68Ga]Ga-NOTA-PSMA-Cy5,并在体外表现出良好的荧光性能和稳定性。通过流式细胞术、荧光成像和LNCaP细胞和PC-3细胞中的细胞摄取实验评估[68Ga]Ga-NOTA-PSMA-Cy5与PSMA的结合特异性。体内 PET/NIRF 成像研究证明 [68Ga]Ga-NOTA-PSMA-Cy5 与 PSMA 具有灵敏且特异性的结合。总体而言,PET/NIRF 双模态探针 [68Ga]Ga-NOTA-PSMA-Cy5 在前列腺癌的诊断以及手术过程中荧光引导下识别 PSMA 阳性癌症病变方面显示出良好的前景。
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 NOTA-PSMA-Cy5 was synthesized via automated solid-phase oligonucleotide synthesis. Subsequently, the PET/NIRF dual-modality probe [68Ga]Ga-NOTA-PSMA-Cy5 was successfully prepared and exhibited favorable fluorescence properties and stability in vitro. The binding specificity of [68Ga]Ga-NOTA-PSMA-Cy5 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 [68Ga]Ga-NOTA-PSMA-Cy5 to PSMA. Overall, the PET/NIRF dual-modality probe [68Ga]Ga-NOTA-PSMA-Cy5 shows promise for the diagnosis of prostate cancer and for the fluorescence-guided identification of PSMA-positive cancer lesions during surgical procedures.