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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 16期

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

页码：4819 / 4822

页数：4

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