Synthesis and autoradiographic localization of the dopamine D-1 agonists [11C]SKF 75670 and [11C]SKF 82957 as potential PET radioligands

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, respectuvely, using [11C]methyl iodide in the presence of N-ethyldiisopropylamide. Both radiotracers were purified using a semi-preparative cation exchange HPLC column. Radiochemical yields of 20–75% were obtained (from [11C]methyl iodine, decay-corrected) with a synthesis time of 30–35 min from EOB. The specific activities wer e 700–2500 Ci/mmol (25.9–92.5 GBq/μmol) 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 caudata-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.