title: Synthesis and autoradiographic localization of the dopamine D-1 agonists [11C]SKF 75670 and [11C]SKF 82957 as potential PET radioligands.
abstract: The high affinity benzazepine D1 agonists SKF 75670 and SKF 82957 were labeled with 11C by N-[11C]methylation of SKF 38393 and SKF 81297, respectively, using [11C]methyl iodide in the presence of N-ethyldiisopropylamine. Both radiotracers were purified using a semi-preparative cation exchange HPLC column. Radiochemical yields of 20-75% were obtained (from [11C]methyl iodide, decay-corrected) with a synthesis time of 30-35 min from EOB. The specific activities were 700-2500 Ci/mmol (25.9-92.5 GBq/mumol) at EOS, and the radiochemical purities were > 99%. Autoradiographic studies showed selective binding for both tracers in rat brain regions rich in D1 receptors such as the caudate-putamen, nucleus accumbens, olfactory tubercles and substantia nigra. [11C]SKF 75670 and [11C]SKF 82957 are thus potential PET radioligands for the functional high-affinity state of D1 receptors.
authors.affiliation: PET Centre, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
authors.forename: J N
authors.initials: JN
authors.lastname: DaSilva
authors.forename: A A
authors.initials: AA
authors.lastname: Wilson
authors.forename: J N
authors.initials: JN
authors.lastname: Nobrega
authors.forename: D
authors.initials: D
authors.lastname: Jiwa
authors.forename: S
authors.initials: S
authors.lastname: Houle
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008024:Ligands; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D001552:Benzazepines; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D008024:Ligands; D017447:Receptors, Dopamine D1; C052506:SK&F 75670; C099238:SKF 82957