N-（2-^18F-氟丙酰基）-L-谷氨酰胺的合成及生物学分布  

Synthesis of N-（ 2-is F-fluoropropionyl）-L-glutamine and its biodistribution study in mice

作　　者：唐彩华[1] 唐刚华[1] 高思远[1] 刘少玉[1] 文富华[1] 聂大红[1] 

机构地区：[1]中山大学附属第一医院核医学科PET/CT中心,广州510080

出　　处：《中华核医学与分子影像杂志》2016年第2期112-115,共4页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金（81571704,81371584）;广东省科技计划基金（2014A020210008）;广东省医学科学基金（A2015378）

摘　　要：目的 合成N端标记新型肿瘤亚氨基酸类PET显像剂N－（2－^18F－氟丙酰基）－L－谷氨酰胺（^18F－FPGLN），并进行正常小鼠及荷PC－3前列腺癌裸鼠体内生物学分布研究。方法 首先在18F多功能合成仪中合成辅基2－^18F－氟丙酸对－硝基苯酯（18F－NFP），^18F－NFP经半制备HPLC纯化后，与L－谷氨酰胺叔丁酯耦联，生成^18F－FPGLN叔丁酯，再经HCl水解，NaOH中和后得到^18F－FPGLN。分别在正常昆明小鼠及荷PC－3前列腺癌裸鼠体内进行生物学分布研究。结果 经多步反应，成功制成^18F－FPGLN示踪剂，其未衰减校正放化产率为10%～15%，放化纯大于96%，总放化合成时间约为130 min。昆明小鼠体内生物分布表明，^18F－FPGLN主要经肾脏代谢，5、120 min时的放射性摄取值分别为（35.0±1.2）和（1.5±0.3） %ID/g。肝、肺、心、小肠等器官放射性摄取相对较低，胰、肌肉、脾、胃、脑放射性摄取很少，其中脑放射性摄取最低，30 min时仅为（1.5±0.3） %ID/g。荷PC－3前列腺癌裸鼠生物分布结果表明，静脉注射^18F－FPGLN后60 min，肿瘤对^18F－FPGLN的摄取明显高于肌肉组织，肿瘤/肌肉比值为2.07。结论成功制备了具备良好药代动力学特性的^18F－FPGLN，为后续肿瘤PET显像研究奠定了基础。Objective To synthesize ^18F labeled N-（2-^18F-fluoropropionyl）-L-glutamine（^18F-FPGLN） for tumor PET imaging, and to perform its biodistribution study on normal mice and PC-3 tumor-bearing nude mice.Methods 4-nitrophenyl-2-^18F-fluoropropionate （^18F-NFP） was synthesized on the MF-2V-IT-I synthesizer and was purified by semi-preparative HPLC. Anhydrous 18F-NFP was added to a solution of L-glutanine t-butyl ester to synthesize ^18F-FPGLN t-butyl ester, which was hydrolyzed by HCl （3 mol/L） and neutralized with NaOH （2 mol/L） solution. 18F-FPGLN product was collected for further study. Biodistribution study was performed on normal Kunming mice and PC-3 prostate cancer tumor-bearing nude mice, respectively.Results ^18F-FPGLN was synthesized with 10%-15% （decay uncorrected） overall radiochemical yield after 130 min of radiosynthesis. The radiochemical purity was higher than 96%. Rapid and high uptake of radiotracer was observed within the kidneys, and was quickly excreted through the urinary bladder. The uptake in kidney reached （35.0±1.2） %ID/g at 5 min post-injection, and descended to （1.5±0.3） %ID/g at 120 min. The liver, lung, heart and small intestine showed relatively moderate uptake of radioactivity. The uptake in the pancreas, muscle, spleen, stomach and brain was low, and the lowest uptake of （1.5±0.3） %ID/g was found in the brain at 30 min post injection. High accumulation of ^18F-FPGLN in PC-3 xenograft was observed, and the tumor/muscle ratio reached 2.07 at 60 min post injection.Conclusion A novel N-position ^18F-labeled glutamine analogs ^18F-FPGLN, with favorable pharmacokinetic characteristics, is synthesized successfully, which makes it possible to perform tumor PET imaging using ^18F-FPGLN subsequently.

关 键 词：谷氨酰胺 同位素标记 氟放射性同位素 前列腺肿瘤 肿瘤移植 小鼠 

分 类 号：R730.4[医药卫生—肿瘤]