Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Bioorg Med Chem. 2011 Jan 1;19(1):102-10. doi: 10.1016/j.bmc.2010.11.048. Epub 2010 Nov 25.
The purpose of this study was to synthesize 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline ([(18)F]FPTQ, [(18)F]7a) and to evaluate its potential as a positron emission tomography ligand for imaging metabotropic glutamate receptor type 1 (mGluR1) in the rat brain. Compound [(18)F]7a was synthesized by [(18)F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline (7b) with potassium [(18)F]fluoride. At the end of synthesis, 1280-1830MBq (n=8) of [(18)F]7a was obtained with >98% radiochemical purity and 118-237GBq/μmol specific activity using 3300-4000MBq of [(18)F]F(-). In vitro autoradiography showed that [(18)F]7a had high specific binding with mGluR1 in the rat brain. Biodistribution study using a dissection method and small-animal PET showed that [(18)F]7a had high uptake in the rat brain. The uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1-selective ligand JNJ-16259685 (2), indicating that [(18)F]7a had in vivo specific binding with mGluR1. Because of a low amount of radiolabeled metabolite present in the brain, [(18)F]7a may have a limiting potential for the in vivo imaging of mGluR1 by PET.
本研究旨在合成 6-[1-(2-[(18)F]氟-3-吡啶基)-5-甲基-1H-1,2,3-三唑-4-基]喹啉([(18)F]FPTQ，[(18)F]7a)，并评估其作为正电子发射断层扫描配体在大鼠脑内成像代谢型谷氨酸受体 1(mGluR1)的潜力。化合物[(18)F]7a 通过用钾[(18)F]氟化物对 6-[1-(2-溴-3-吡啶基)-5-甲基-1H-1,2,3-三唑-4-基]喹啉(7b)进行[(18)F]氟化反应合成。在合成结束时，从 3300-4000MBq 的[(18)F]F(-)中获得 1280-1830MBq(n=8)的[(18)F]7a，放射化学纯度>98%，比活度为 118-237GBq/μmol。体外放射自显影显示[(18)F]7a 在大鼠脑中与 mGluR1 具有高特异性结合。使用解剖方法和小动物 PET 的生物分布研究表明，[(18)F]7a 在大鼠脑中具有高摄取。放射性物质在小脑的摄取被未标记的 7a 和 mGluR1 选择性配体 JNJ-16259685(2)降低，表明[(18)F]7a 在体内与 mGluR1 具有特异性结合。由于脑内存在少量放射性标记代谢物，[(18)F]7a 可能限制了 PET 对 mGluR1 的体内成像。
