title: Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane.
abstract: We report here a radiosynthesis for the D(2/3) agonist (+)-4-([3-(11)C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (3-[(11)C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on (11)C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH(4) to give ([3-(11)C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([(11)C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77-97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3-(11)C]-(+)-PHNO) in 55-60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3-(11)C]PHNO with an average radiochemical yield of 9% (n=13, range 2-30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8-81.1 GBq/μmol in a total time of 63-65 min.
authors.affiliation: Molecular Therapy Group, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Segundo
authors.initials: S
authors.lastname: Francisco Garcia-Arguello
authors.forename: Robin
authors.initials: R
authors.lastname: Fortt
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Steel
authors.forename: Diana
authors.initials: D
authors.lastname: Brickute
authors.forename: Matthias
authors.initials: M
authors.lastname: Glaser
authors.forename: David R
authors.initials: DR
authors.lastname: Turton
authors.forename: Edward G
authors.initials: EG
authors.lastname: Robins
authors.forename: Erik
authors.initials: E
authors.lastname: Arstad
authors.forename: Sajinder K
authors.initials: SK
authors.lastname: Luthra
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists*
chemical_list: D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D010078:Oxazines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C014055:methyl iodide