Automatic radiosynthesis and preclinical evaluation of F-18-AlF-PSMA-NF as a potential PET probe for prostate cancer imaging
Automatic radiosynthesis and preclinical evaluation of F-18-AlF-PSMA-NF as a potential PET probe for prostate cancer imaging
复制标题
18F-AlF-PSMA-NF 作为前列腺癌成像潜在 PET 探针的自动放射合成和临床前评估
DOI：
10.1007/s00726-021-02997-7
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Wu Hubing
中科院分区：
文献类型：
--
作者：
Zhou Wenlan;Huang Shun;Jiang Yanping;Hu Kongzhen;Wang Lijuan;Han Yanjiang;Wu Hubing
前列腺特异性膜抗原（PSMA）示踪剂的自动化生产对于其临床应用具有重要意义。本研究以二甲基甲酰胺（DMF）为溶剂，在正电子发射断层扫描仪（PET）-MF-2 V-IT-I上，采用自动化方法制备了18F-AlF-PSMA-NF，并对该探针的自动化制备方法和临床应用价值进行了探讨。在体外和体内检查示踪剂特性。18F-AlF-PSMA-NF在35 min内自动制备，无衰减校正产率为37.9 ± 11.2%。该示踪剂具有亲水性，对PSMA有很高的亲和力，在细胞实验中，PSMA阳性的LNCaP细胞对18F-AlF-PSMA-NF的摄取量显著高于PSMA阴性的PC-3细胞PSMA抑制剂ZJ-43-a可阻断上述作用（P< 0.001）。18F-AlF-PSMA-NF在micro-PET/CT上清楚地显示了LNCaP肿瘤，具有高水平的摄取（13.72 ± 2.01%注射剂量/克组织[%ID/g]）和高肿瘤/肌肉比（接近50：1）。PSMA阳性的LNCaP肿瘤细胞摄取LNCaP蛋白的能力明显高于PSMA阴性的PC-3肿瘤细胞（13.72 ± 2.01%ID/gvs.1.07 ± 0.48%ID/g，t= 10.382，P < 0.001），并能被ZJ-43阻断（13.72 ± 2.01%ID/gvs.2.77 ± 1.44%ID/g，t= 8.14，P < 0.001）。成功研制了一种新的18F-AlF标记PSMA探针--18F-AlF-PSMA-NF-。它具有类似于基于PSMA的探针的生物学特征，并且有可能用于临床环境。
Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—and explore its automated production method and potential value in clinical settings.18F-AlF-PSMA-NF was prepared using an automated method with dimethylformamide (DMF) as the solvent in a positron emission tomography (PET)-MF-2 V-IT-I synthesizer. Tracer characteristics were examined both in vitro and in vivo. Micro-PET/computed tomography (CT) was performed to investigate the utility of18F-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo.18F-AlF-PSMA-NF was prepared automatically within 35 min with a non-attenuation correction yield of 37.9 ± 11.2%. The tracer was hydrophilic, had a high affinity for PSMA (Kd = 2.58 ± 0.81 nM), and showed stability in both in vitro and in vivo conditions.In the cellular experiments,18F-AlF-PSMA-NF uptake in PSMA-positive LNCaP cells was significantly higher than that in PSMA-negative PC-3 cells (P< 0.001), and could be blocked by excess ZJ-43—a PSMA inhibitor (P< 0.001). LNCaP tumours were clearly visualized by18F-AlF-PSMA-NF on micro-PET/CT, with a high level of uptake (13.72 ± 2.01 percent injected dose per gram of tissue [%ID/g]) and high tumour/muscle ratio (close to 50:1). The PSMA-positive LNCaP tumours had a significantly higher uptake than PSMA-negative PC-3 tumours(13.72 ± 2.01%ID/gvs.1.07 ± 0.48%ID/g,t= 10.382,P< 0.001), and could be blocked by ZJ-43 (13.72 ± 2.01%ID/gvs.2.77 ± 1.44%ID/g,t= 8.14,P< 0.001). A new18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—was successfully developed and can be prepared automatically. It has the biological characteristics resembling that of a PSMA-based probe and can potentially be used in clinical settings.