Department of NanFang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China.
Amino Acids. 2021 Jun;53(6):929-938. doi: 10.1007/s00726-021-02997-7. Epub 2021 May 20.
Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new F-AlF-labelled PSMA probe-F-AlF-PSMA-NF-and explore its automated production method and potential value in clinical settings. F-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 of F-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo. F-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, F-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 by F-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/g vs. 1.07 ± 0.48%ID/g, t = 10.382, P < 0.001), and could be blocked by ZJ-43 (13.72 ± 2.01%ID/g vs. 2.77 ± 1.44%ID/g, t = 8.14, P < 0.001). A new F-AlF-labelled PSMA probe-F-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.
自动生产对于前列腺特异性膜抗原（PSMA）示踪剂在临床实践中的应用很重要。我们开发了一种新的 F-AlF 标记的 PSMA 探针 F-AlF-PSMA-NF，并探索了其在临床环境中的自动化生产方法和潜在价值。F-AlF-PSMA-NF 是使用二甲亚砜（DMF）作为溶剂，在正电子发射断层扫描（PET）-MF-2 V-IT-I 合成仪中使用自动化方法制备的。在体外和体内均检查了示踪剂的特性。进行微 PET/计算机断层扫描（CT）以研究 F-AlF-PSMA-NF 用于体内成像 PSMA 阳性肿瘤的效用。F-AlF-PSMA-NF 在 35 分钟内自动制备，非衰减校正产率为 37.9±11.2%。该示踪剂具有亲水性，对 PSMA 具有高亲和力（Kd=2.58±0.81 nM），并且在体外和体内条件下均稳定。在细胞实验中，F-AlF-PSMA-NF 在 PSMA 阳性 LNCaP 细胞中的摄取明显高于 PSMA 阴性 PC-3 细胞（P<0.001），并且可以被过量的 ZJ-43-a PSMA 抑制剂阻断（P<0.001）。F-AlF-PSMA-NF 在微 PET/CT 上可清晰显示 LNCaP 肿瘤，摄取水平高（13.72±2.01 ％注入剂量/克组织[％ID/g]），肿瘤/肌肉比高（接近 50:1）。与 PSMA 阴性 PC-3 肿瘤相比，PSMA 阳性 LNCaP 肿瘤的摄取明显更高（13.72±2.01％ID/g 比 1.07±0.48％ID/g，t=10.382，P<0.001），并且可以被 ZJ-43 阻断（13.72±2.01％ID/g 比 2.77±1.44％ID/g，t=8.14，P<0.001）。成功开发了一种新的 F-AlF 标记的 PSMA 探针 F-AlF-PSMA-NF，可以自动制备。它具有类似于 PSMA 探针的生物学特性，可能在临床环境中使用。
