Park Jun Young, Son Jeongmin, Yun Mijin, Ametamey Simon M, Chun Joong-Hyun
Department of Nuclear Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Labelled Comp Radiopharm. 2018 Jan;61(1):30-37. doi: 10.1002/jlcr.3566. Epub 2017 Dec 22.
(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[ F]-fluoroethoxy)propyl) oxime ([ F]-(E)-PSS232, [ F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu ) in vivo. The mGlu has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11-labeled and fluorine-18-labeled radiotracers have been developed to measure mGlu receptor occupancy in the human brain. The radiotracer [ F]2a, which is used as an analogue for [ C]ABP688 ([ C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu . Herein, we report the fully automated radiosynthesis of [ F]2a using a commercial GE TRACERlab™ FX- synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [ F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [ F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [ F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes.
（E）-3-（吡啶-2-基乙炔基）环己-2-烯酮O-（3-（2-[¹⁸F] -氟乙氧基）丙基）肟（[¹⁸F] -（E）-PSS232，[¹⁸F] 2a）是一种最近开发的放射性示踪剂，可用于在体内可视化代谢型谷氨酸受体5（mGlu₅）。由于mGlu₅在许多神经精神疾病中起作用，它已成为一个有吸引力的治疗和诊断靶点。已经开发了几种碳-11标记和氟-18标记的放射性示踪剂来测量人脑中的mGlu₅受体占有率。放射性示踪剂[¹⁸F] 2a用作[¹¹C]ABP688（[¹¹C] 1）的类似物，并且具有更长的物理半衰期，是一种对mGlu₅表现出高结合亲和力的选择性放射性示踪剂。在此，我们报告了使用商业通用电气TRACERlab™FX合成仪对[¹⁸F] 2a进行全自动放射性合成，用于常规生产并分发给附近的卫星诊所。在100°C下于二甲基亚砜（DMSO）中，用回旋加速器产生的[¹⁸F]氟离子对相应的甲磺酸酯前体进行亲核取代，然后进行高效液相色谱（HPLC）纯化和制剂配制，在合成结束时很容易得到放射性化学产率为40±2％（衰变校正，n = 5）的[¹⁸F] 2a。[¹⁸F] -（E）-构象体的放射性化学纯度大于95％。摩尔活度测定为63.6±9.6 GBq/μmol（n = 5），总合成时间为70分钟。
