title: Synthesis of 6-[¹⁸F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET.
abstract: 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-[(18)F]fluoro-PBR28 (>95% radiochemically pure). Non-decay-corrected overall yields were 9-10% and specific radioactivities ranged from 74 to 148 GBq/μmol. In vitro binding experiments, dynamic μPET 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-[(18)F]fluoro-PBR28 to image the TSPO 18 kDa using PET.
authors: CEA, I²BM, Service Hospitalier Frédéric Joliot, Orsay, France. annelaure.damont@cea.fr
authors: Annelaure
authors: A
authors: Damont
authors: Raphaël
authors: R
authors: Boisgard
authors: Bertrand
authors: B
authors: Kuhnast
authors: Frédéric
authors: F
authors: Lemée
authors: Guillaume
authors: G
authors: Raggiri
authors: Alana M
authors: AM
authors: Scarf
authors: Eleonora
authors: E
authors: Da Pozzo
authors: Silvia
authors: S
authors: Selleri
authors: Claudia
authors: C
authors: Martini
authors: Bertrand
authors: B
authors: Tavitian
authors: Michael
authors: M
authors: Kassiou
authors: Frédéric
authors: F
authors: Dollé
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D008024:Ligands; D057054:Molecular Imaging; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D018079:Receptors, GABA / Q000737:chemistry*; D013237:Stereoisomerism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D000081:Acetamides; D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D008024:Ligands; C568083:N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid