18F-FAPI-42的自动化合成及小动物PET/CT显像研究

Automated Radiosynthesis and Micro PET/CT Imaging of 18F-FAPI-42

  • 摘要: 成纤维细胞活化蛋白(fibroblast activation protein, FAP)在多数上皮来源恶性肿瘤中高度表达,FAP抑制剂(FAPI)经核素标记后已用于肿瘤的早期诊断。为实现PET显像剂18F-FAPI-42的自动化合成并进行质量控制,本研究基于Allinone合成器及其配套的空白试剂盒,通过一锅反应自动化制备18F-FAPI-42,并在荷胶质母细胞瘤U87-MG模型鼠行小动物PET/CT(positron emission tomography/computed tomography) 动态显像对其进行评价。结果显示,18F-FAPI-42的自动化合成时间在60 min以内,放化产率为(15.8±3.2)%(n=10,未经衰变校正),放化纯度>95 %,比活度14~52 GBq/μmol。小动物PET/CT动态显像显示,18F-FAPI-42对肿瘤显影清晰,放射性滞留时间长,具有较高的肿瘤与肌肉摄取比,活度与时间曲线显示其主要通过肾脏排泄。以上结果表明,Allinone合成器能够稳定高效地合成符合药物质控标准的18F-FAPI-42,所得产品质量满足临床要求。该合成方法可为NOTA类修饰化合物的18F标记提供参考和借鉴。

     

    Abstract: Fibroblast activation protein is highly expressed in most epithelial malignant tumors. FAP inhibitor (FAPI) has been used in the early diagnosis of tumors after radionuclide labeling. Objective to achieve automated synthesis and quality control of PET imaging agent 18F-FAPI-42. This study was based on the Allinone synthesizer and its accompanying blank kit, and 18F-FAPI-42 was prepared through one-pot reaction automation. Then, Positron Emission Tomography/Computed Tomography (PET/CT) dynamic imaging was performed on the U87-MG model mouse bearing glioblastoma to evaluate its value. The automated synthesis time of 18F-FAPI-42 was within 60 minutes, with a yield of (15.8±3.2)% (n=10, without decay correction), radiochemical purity than 95%, and specific activity of 14.52 GBq/μmol. micro PET/CT dynamic imaging showed that 18F-FAPI-42 had clear tumor development, long radiation retention time, high tumor to muscle uptake ratio, and activity time curve showed that it was mainly excreted through the kidney. The Allinone synthesizer can stably and efficiently synthesize 18F-FAPI-42 that meets drug quality control standards, and the resulting product quality meets clinical requirements. This synthesis method can provide reference and guidance for 18F labeling of NOTA modified compounds.

     

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