18F-DCFPyL的制备和初步临床应用

Automatically synthesize the prostate-specific membrane antigen (PSMA) imaging agent 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridin-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) using a domestic fluorine multi-functional module and conduct biological evaluations. By changing different hydrolysis conditions, study the hydrolysis efficiency of the fluorinated intermediate, conduct quality control and biosafety evaluation on 18F-DCFPyL, and explore the biological properties of 18F-DCFPyL through the biological distribution in mice and preliminary clinical trials. A patient with biochemical recurrence after prostate cancer surgery underwent 18F-DCFPyL PET/CT imaging. The results showed that the hydrolysis efficiencies of three acids, H3PO4, HCl, and HI, were similar, being 17.1%, 16.9%, and 18.4% respectively. The radiochemical purity of the obtained product was greater than 98%, and the specific activity was 54 - 90 GBq/μmol. 18F-DCFPyL was excreted through the urinary system in mice, and there was no significant uptake in other tissues. In a patient with biochemical recurrence after prostate cancer surgery, 18F-DCFPyL PET imaging could detect small metastatic lesions that could not be detected by CT on the same machine. The domestic fluorine multi-functional module has high stability and repeatability in the automatic synthesis of 18F-DCFPyL, and the product quality meets the requirements of clinical research. 18F-DCFPyL has good biological distribution characteristics and can be used for the early diagnosis of prostate cancer and the detection of lesions in patients with biochemical recurrence of prostate cancer.

：利用国产氟多功能模块自动化合成前列腺特异性膜抗原（PSMA）显像剂18F-DCFPyL（２－（３－｛１－羧基－５－［（６－［１８Ｆ］氟－吡啶－３－羰基）－胺基］－戊基｝－脲基）－戊二酸）并进行生物学评价。通过改变不同的水解条件，研究氟化中间体的水解效率，对１８Ｆ－ＤＣＦＰｙＬ进行质量控制和生物安全性评价，并通过小鼠生物学分布和初步临床试验探讨１８Ｆ－ＤＣＦＰｙＬ的生物学性质，一例生化复发的前列腺癌术后患者进行了１８ＦＤＣＦＰｙＬ ＰＥＴ／ＣＴ显像。结果表明，Ｈ３ＰＯ４、ＨＣｌ和ＨＩ三种酸的水解效率相近，分别为１７．１％、１６．９％和１８．４％，得到产品放化纯度均大于９８％，比活度为５４～９０ＧＢｑ／μｍｏｌ，１８Ｆ－ＤＣＦＰｙＬ在小鼠体内经泌尿系统排泄，其余组织无明显摄取，前列腺癌术后生化复发的患者１８Ｆ－ＤＣＦＰｙＬ ＰＥＴ显像能够探查同机ＣＴ无法检出的微小转移灶。国产氟多功能模块自动化合成１８Ｆ－ＤＣＦＰｙＬ的稳定性和重复性高，产品质量符合临床研究要求，１８Ｆ－ＤＣＦＰｙＬ具有良好的生物学分布特性，可用于早期诊断前列腺癌及探测前列腺癌生化复发患者的病灶。