Brooks Allen F, Mufarreh Anthony J, Shao Xia, Kaur Tanpreet, Stauff Jenelle, Arteaga Janna, Kilbourn Michael R, Scott Peter J H
Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Med Chem Lett. 2020 Aug 28;11(11):2300-2304. doi: 10.1021/acsmedchemlett.0c00419. eCollection 2020 Nov 12.
The radiotracers [C]COU and [C]PHXY are potential PET imaging agents for in vivo studies of monoamine oxidases (MAOs), as previously shown in rodent and primate brain. One-pot, automated methods for the radiosynthesis of [C]PHXY and [C]COU were developed to provide reliable and improved radiochemical yields. Although derived from the structure of the neurotoxin MPTP, COU did not exhibit in vivo neurotoxicity to dopaminergic nerve terminals in the mouse brain as assayed by losses of VMAT2 radioligand binding. PET imaging studies in rats demonstrated that both [C]COU and [C]PHXY exhibit retention in cardiac tissues that can be blocked by pretreatment with the MAO inhibitors deprenyl (MAO-B) and pargyline (MAO-A and -B). In addition to prior neuroimaging applications, [C]COU and [C]PHXY are thus also of interest for studies of MAO enzymatic activity and imaging of sympathetic nerve density in heart.
放射性示踪剂[C]COU和[C]PHXY是用于单胺氧化酶（MAO）体内研究的潜在正电子发射断层扫描（PET）成像剂，如先前在啮齿动物和灵长类动物大脑中所示。已开发出一锅法自动化方法用于[C]PHXY和[C]COU的放射性合成，以提供可靠且提高的放射化学产率。尽管COU源自神经毒素MPTP的结构，但通过VMAT2放射性配体结合损失测定，其在小鼠大脑中对多巴胺能神经末梢未表现出体内神经毒性。在大鼠中的PET成像研究表明，[C]COU和[C]PHXY在心脏组织中均有滞留，可通过用MAO抑制剂丙炔苯丙胺（MAO-B）和优降宁（MAO-A和-B）预处理来阻断。除了先前的神经成像应用外，[C]COU和[C]PHXY因此也可用于MAO酶活性研究和心脏交感神经密度成像。
