N-(2-chloro-5-(S-2-[18F]fluoroethyl)thiophenyl)-N'-(3-thiomethylphenyl)-N'-methylguanidine, ([18F]GE-179), has been identified as a promising positron emission tomography (PET) ligand for the intra-channel phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor. The radiosynthesis of [18F]GE-179 has only been performed at low radioactivity levels. However, the manufacture of a GMP compliant product at high radioactivity levels was required for clinical studies. We describe the development of a process using the GE FASTlab™ radiosynthesis platform coupled with HPLC purification. The radiosynthesis is a two-step process, involving the nucleophilic fluorination of ethylene ditosylate, 11, followed by alkylation to the deprotonated thiol precursor, N-(2-chloro-5-thiophenol)-N'-(3-thiomethylphenyl)-N'-methyl guanidine, 8. The crude product was purified by semi-preparative HPLC to give the formulated product in an activity yield (AY) of 7 ± 2% (n = 15) with a total synthesis time of 120 minutes. The radioactive concentration (RAC) and radiochemical purity (RCP) were 328 ± 77 MBq/mL and 96.5 ± 1% respectively and the total chemical content was 2 ± 1 μg. The final formulation volume was 14 mL. The previously described radiosynthesis of [18F]GE-179 was successfully modified to deliver an process on the FASTlab™ that allows the manufacture of a GMP quality product from high starting radioactivitity (up to 80 GBq) and delivers a product suitable for clinical use.
N-(2-
氯-5-(S-2-[18F]
氟乙基)噻苄基)-N'-(3-
硫甲基苯基)-N'-甲基
胍([18F]GE-179)已被确定为一种有前景的正电子发射断层扫描(PET)
配体,用于
N-甲基-D-天冬氨酸(N
MDA)受体的通道内苯环神经
磷(PCP)结合位点。[18F]GE-179的放射合成仅在低放射活度
水平下进行。然而,为了进行临床研究,需要制造出符合GMP标准的高放射活度产品。我们描述了一种使用GE FASTlab™放射合成平台结合HPLC纯化的工艺开发。放射合成是一个两步过程,涉及对
乙烯二托烯
磺酸酯11的核取代
氟化,随后对去质子化的
硫醇前体,N-(2-
氯-5-噻
苄醇)-N'-(3-
硫甲基苯基)-N'-甲基
胍8进行烷基化。粗产品通过半制备HPLC进行纯化,得到的制剂产品放射活度产率(AY)为7 ± 2%(n = 15),总合成时间为120分钟。放射性浓度(RAC)和放射
化学纯度(RCP)分别为328 ± 77 MBq/mL和96.5 ± 1%,总
化学含量为2 ± 1 μg。最终制剂体积为14 mL。之前描述的[18F]GE-179的放射合成成功地进行修改,从而在FASTlab™上提供了一种工艺,使得可以从高起始放射活度(最多80 GBq)制造出GMP品质的产品,最终产品适合临床使用。