This is the first human trial study, and the team successfully synthesized a high dose of [18F] AlF-P16-093 under GMP conditions, with a radiochemical purity of>95% and an average labeling yield of 36.5 ± 8.3% (n=12). The results of radiation dosimetry research indicate that the radiopharmaceutical is observed to have high uptake in the kidneys, spleen, and liver, with a systemic effective dose of 16.8 ± 1.3 μ Sv/MBq, 30% lower than [68Ga] Ga-P16-093. All subjects had good tolerance to PET examination and no adverse events were observed. Preliminary diagnostic studies have shown that [18F] AlF-P16-093 uptake is rapid in PSMA positive tumors and can be detected within 10 minutes. Subsequently, multiple time point scans did not show any other lesions. Each patient has at least one detectable tumor lesion, with a total of 356 tumor lesions observed, including intra prostate, lymph node, bone, and other soft tissue metastases.

       The results of this study indicate that [18F] AlF-P16-093 is safe and the radiation dose is acceptable. Preliminary diagnostic studies have shown that it has the potential to be widely used in the diagnosis of prostate cancer patients.

Figure: MIP images of AlF-P16-093 at different time points [18F] after injection. b) PET/CT sagittal images of prostate tumors at different times after injection. The arrow indicates the location of the prostate tumor. 10 minutes after injection, the lesions inside the prostate are clearly visible.

Figure: Compared with [68Ga]Ga-PSMA-11 (d-f) and mpMRI (g-j), [18F]AlF-P16-093 (a-c) was effective in detecting primary lesions in the prostate.

       In addition, our team also performed [18F]AlF-P16-093 PET/CT dynamic scans on 8 patients with primary prostate cancer (PPCa). Through the analysis of dynamic time-activity curves (TAC) of tumors and normal tissues, the optimal pharmacokinetic model (2T4K) was determined, and based on the correlation between the total volume of distribution (Vt) and static uptake measurements obtained from this model, a simplified quantitative method was determined to approximate the value of Vt using SURmean (the ratio of tumor SUVmean to blood SUVmean) over a time window of 28-34 minutes. The results showed that the method could effectively characterize the tumor burden of PPCa patients, with a high degree of consistency and correlation with the results of manual labeling, and also had a significant correlation with serum prostate-specific antigen (tPSA) levels.

Figure: 0-60min dynamic imaging MIP diagram and 120min delayed whole body imaging MIP diagram.

Figure: a) Plot of correlation between SURmean sampled at scan and Vt calculated from the whole chamber model. b) The average SUM value at 28 min after injection was significantly correlated with Vt

       The two studies not only explored the dosimetry, safety, and preliminary diagnostic efficacy of [18F]AlF-P16-093, but also further evaluated its optimal kinetic model among the three atrioventricular models. This study not only provides theoretical support for the precise application of the drug, but also establishes a simplified quantitative method for the calculation of alternative kinetic models, which lays the foundation for the wide clinical application of the drug. The research results were published in the European Journal of Nuclear Medicine and Molecular Imaging at the same time.