Automatic radiosynthesis and preclinical evaluation of 18F-AlF-PSMA-NF as a potential PET probe for prostate cancer imaging

摘要

Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new F-18-AlF-labelled PSMA probe-F-18-AlF-PSMA-NF-and explore its automated production method and potential value in clinical settings. F-18-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-18-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo. F-18-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-18-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-18-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-18-AlF-labelled PSMA probe-F-18-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.

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