18F-DCFPyL的制备和初步临床应用

Preparation and Clinical Application of 18F-DCFPyL

  • 摘要: 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18F-DCFPyL 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54~90 GBq/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。

     

    Abstract: 18F-DCFPyL, a PSMA-based PET imaging agent for prostate cancer, was auto synthesized and evaluated. Following the direct nucleophilic heteroaromatic substitution with 18Ffluoride at the ortho-position of precursor, the deprotection of the ester moieties of the intermediate with different acids was attempted to obtain a good hydrolysis yield. The biodistribution in normal NIH mice and PET/CT imaging for a patient with biochemical recurrence of prostate cancer were also performed. The results showed that no remarkable discrepancy of the hydrolysis efficiency was found among three kinds of acids, H3PO4, HCl and HI, which were 17.1%, 16.9% and 18.4%, respectively with a specific activity of 54 to 90 GBq/μmol. The highest levels of radioactivity in the NIH mice were observed in the kidneys. Meanwhile, the uptake of the tracer in the blood was declined rapidly and a low accumulation of the radio-tracer was observed in most of the other organs. 18F-DCFPyL PET imaging for a postoperative patient with biochemical recurrence of prostate cancer can detect small metastatic foci that can not be detected by the CT. 18F-DCFPyL was synthesized reliably and repeatedly by domestic synthesis module and it passed the quality control. It has satisfactory properties in vivo and is probably suitable for early diagnosis of prostate cancer and detection of lesions in patients with biochemical recurrence of prostate cancer.

     

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