SYNTHESIS AND AUTORADIOGRAPHIC LOCALIZATION OF THE DOPAMINE D-1 AGONISTS [C-11]SKF-75670 AND [C-11]SKF-82957 AS POTENTIAL PET RADIOLIGANDS

The high affinity benzazepine D-1 agonists SKF 75670 and SKF 82957 wer e labeled with C-11 by N-[C-11]methylation of SKF 38393 and SKF 81297, respectively, using [C-11]methyl iodide in the presence of N-ethyldii sopropylamine. Both radiotracers were purified using a semi-preparativ e cation exchange HPLC column. Radiochemical yields of 20-75% were obt ained (from [C-11]methyl iodide, decay-corrected) with a synthesis tim e of 30-35 min from EOB. The specific activities were 700-2500 Ci/mmol (25.9-92.5 GBq/mu mol) at EOS, and the radiochemical purities were >9 9%. Autoradiographic studies showed selective binding for both tracers in rat brain regions rich in D-1 receptors such as the caudate-putame n, nucleus accumbens, olfactory tubercles and substantia nigra. [C-11] SKF 75670 and [C-11]SKF 82957 are thus potential PET radioligands for the functional high-affinity state of D-1 receptors.