Synthesis of 6-[18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET

被引:24
作者
Damont, Annelaure [1 ]
Boisgard, Raphael [1 ,2 ]
Kuhnast, Bertrand [1 ]
Lemee, Frederic [1 ]
Raggiri, Guillaume [1 ]
Scarf, Alana M. [3 ,4 ]
Da Pozzo, Eleonora [5 ]
Selleri, Silvia [6 ]
Martini, Claudia
Tavitian, Bertrand [1 ,2 ]
Kassiou, Michael [4 ,7 ,8 ]
Dolle, Frederic [1 ]
机构
[1] CEA, Serv Hosp Frederic Joliot, I2BM, F-91406 Orsay, France
[2] Univ Paris 11, INSERM, U1023, Lab Imagerie Mol Expt, F-91405 Orsay, France
[3] Univ Sydney, Discipline Pharmacol, Sydney, NSW 2006, Australia
[4] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2050, Australia
[5] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56100 Pisa, Italy
[6] Univ Florence, Dept Pharmaceut Sci, I-50121 Florence, Italy
[7] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia
[8] Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006, Australia
关键词
Translocator protein (TSPO); Radioligand; Fluorine-18; PET tracer; Neuroinflammation; PERIPHERAL BENZODIAZEPINE-RECEPTOR; PHENOXYPHENYL-ACETAMIDE DERIVATIVES; IN-VIVO BINDING; NONHUMAN-PRIMATES; RADIOLIGAND; LIGANDS; BRAIN; RADIOSYNTHESIS; MONKEY; DAA1097;
D O I
10.1016/j.bmcl.2011.06.048
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
6-Fluoro-PBR28 (N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl) acetamide), a fluorinated analogue of the recently developed TSPO 18 kDa ligand PBR28, was synthesized and labelled with fluorine- 18. 6-Fluoro-PBR28 and its 6-chloro/6-bromo counterparts were synthesized in six chemical steps and obtained in 16%, 10% and 19% overall yields, respectively. Labelling with fluorine-18 was performed in one single step (chlorine/bromine-for-fluorine heteroaromatic substitution) using a Zymate-XP robotic system affording HPLC-purified, ready-to-inject, 6-[F-18] fluoro-PBR28 (> 95% radiochemically pure). Non-decay-corrected overall yields were 9-10% and specific radioactivities ranged from 74 to 148 GBq/mu mol. In vitro binding experiments, dynamic mu PET studies performed in a rat model of acute neuroinflammation (unilaterally, AMPA-induced, striatum-lesioned rats) and ex vivo autoradiography on the same model demonstrated the potential of 6-[F-18] fluoro-PBR28 to image the TSPO 18 kDa using PET. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4819 / 4822
页数:4
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