Automated Synthesis of (rac)-, (R)-, and (S)-[18 F]Epifluorohydrin and Their Application for Developing PET Radiotracers Containing a 3-[18 F]Fluoro-2-hydroxypropyl Moiety.
To introduce the 3-[18 F]fluoro-2-hydroxypropyl moiety into positron emission tomography (PET) radiotracers, we performed automated synthesis of (rac)-, (R)-, and (S)-[18 F]epifluorohydrin ([18 F]1) by nucleophilic displacement of (rac)-, (R)-, or (S)-glycidyl tosylate with 18 F- and purification by distillation. The ring-opening reaction of (R)- or (S)-[18 F]1 with phenol precursors gave enantioenriched [18 F]fluoroalkylated products without racemisation. We then synthesised (rac)-, (R)-, and (S)- 2-{5-[4-(3-[18 F]fluoro-2-hydroxypropoxy)phenyl]-2-oxobenzo[d]oxazol-3(2H)-yl}-N-methyl-N-phenylacetamide ([18 F]6) as novel radiotracers for the PET imaging of translocator protein (18 kDa) and showed that (R)- and (S)-[18 F]6 had different radioactivity uptake in mouse bone and liver. Thus, (rac)-, (R)-, and (S)-[18 F]1 are effective radiolabelling reagents and can be used to develop PET radiotracers by examining the effects of chirality on their in vitro binding affinities and in vivo behaviour.
['Fujinaga|Masayuki|M|', 'Ohkubo|Takayuki|T|', 'Yamasaki|Tomoteru|T|', 'Zhang|Yiding|Y|', 'Mori|Wakana|W|', 'Hanyu|Masayuki|M|', 'Kumata|Katsushi|K|', 'Hatori|Akiko|A|', 'Xie|Lin|L|', 'Nengaki|Nobuki|N|', 'Zhang|Ming-Rong|MR|0000-0002-3001-9605']
D000818:Animals D001842:Bone and Bones D001921:Brain D004852:Epoxy Compounds D005462:Fluorine Radioisotopes D006845:Hydrocarbons, Fluorinated D051379:Mice D015394:Molecular Structure D049268:Positron-Emission Tomography D020005:Propanols D019275:Radiopharmaceuticals D018079:Receptors, GABA D013237:Stereoisomerism D014018:Tissue Distribution
automated synthesis translocator protein 18F-fluoroalkylation [18F]epifluorohydrin imaging agents