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Synthesis and Evaluation of a New 18F-Labeled Radiotracer for Studying the GABAB Receptor in the Mouse Brain
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-03-02 00:00:00 , DOI: 10.1021/acschemneuro.8b00038
Ravi Naik 1 , Heather Valentine 1 , Robert F. Dannals 1 , Dean F. Wong 1 , Andrew G. Horti 1
Affiliation  

New GABAB agonists, fluoropyridyl ether analogues of baclofen, have been synthesized as potential PET radiotracers. The compound with highest inhibition binding affinity as well as greatest agonist response, (R)-4-amino-3-(4-chloro-3-((2-fluoropyridin-4-yl)methoxy)phenyl)butanoic acid (1b), was radiolabeled with 18F with good radiochemical yield, high radiochemical purity, and high molar radioactivity. The regional brain distribution of the radiolabeled (R)-4-amino-3-(4-chloro-3-((2-[18F]fluoropyridin-4-yl)methoxy)phenyl)butanoic acid, [18F]1b, was studied in CD-1 male mice. The study demonstrated that [18F]1b enters the mouse brain (1% ID/g tissue). The accumulation of [18F]1b in the mouse brain was inhibited (35%) by preinjection of GABAB agonist 1a, suggesting that the radiotracer brain uptake is partially mediated by GABAB receptors. The presented data demonstrate a feasibility of imaging of GABAB receptors in rodents and justify further development of GABAB PET tracers with improved specific binding and greater blood-brain barrier permeability.

中文翻译:

用于研究小鼠脑中GABA B受体的新型18 F标签放射性示踪剂的合成与评价

已经合成了新的GABA B激动剂,巴氯芬的氟吡啶醚类似物,作为潜在的PET放射性示踪剂。具有最高抑制结合亲和力和最大激动剂响应的化合物(R)-4-氨基-3-(4-氯-3-((2-氟吡啶-4--4-基)甲氧基)苯基)丁酸(1b)用18 F放射性标记,具有良好的放射化学收率,较高的放射化学纯度和较高的摩尔放射性。放射性标记的(R)-4-氨基-3-(4-氯-3-((2- [ 18 [ F]氟吡啶-4-基)甲氧基)苯基)丁酸[ 18 F] 1b的区域脑分布在CD-1雄性小鼠中进行了研究。研究表明[ 18F] 1b进入老鼠的大脑(1%ID / g组织)。预先注射GABA B激动剂1a抑制了[ 18 F] 1b在小鼠大脑中的蓄积(35%),表明放射性示踪剂脑的摄取部分由GABA B受体介导。提出的数据证明了在啮齿动物中对GABA B受体成像的可行性,并证明了进一步开发GABA B PET示踪剂具有改善的特异性结合和更大的血脑屏障通透性的合理性。
更新日期:2018-03-02
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