SYNTHESIS AND EVALUATION OF PYLAMINO)-2-HYDROXY-PROPOXY)-2H-BENZIMIDAZOL-2-ONE ((S)-[C-11]CGP12388) AND PYL)AMINO)-2-HYDROXYPROPOXY)-2H-BENZIMIDAZOL-2-ONE ((S)-[F-18]FLUORO-CGP-12388) FOR VISUALIZATION OF BETA-ADRENOCEPTORS WITH POSITRON-EMISSION-TOMOGRAPHY

The beta-adrenoceptor antagonist (S)-[C-11]CGP 12177 (4-(3-(tert-butyl amino)-2-hydroxypropoxy)- 2H-benzimidazol-2[C-11]-one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthe sis of [C-11]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-C GP 12388 ylamino)-2-hydroxypropoxy)-2H-benzimidazol- 2-one), 5, the isopropyl analogue of CGP 12177,has been labeled with c arbon-11 in the isopropyl group via a reductive alkylation by [C-11]ac etone (3) of the corresponding (S)-desisopropyl compound 2. The fluoro -substituted analogue of (S-CGP 12388 was prepared by reacting 2 with [F-18]fluoroacetone (4). (S)-[C-11]CGP 12388 (5) was easily prepared v ia a one-pot procedure. The radiochemical yield of (S)-[C-11]CGP 12388 (600-800 Ci/mmol, EOS) was 18% (EOB) with a total synthesis time of 3 5 min, whereas (S)-[F-18]fluoro-CGP 12388 (6)(>2000 Ci/mmol, EOS) was synthesized in 105 min with a radiochemical yield of 12% (EOB). Biodis tribution studies in rats demonstrated specific binding to beta-adreno ceptors of (S)-[F-18]fluoro-CGP 12388 and (S)-[C-11]CGP 12388 in lung and heart. The lungs were clearly visualized with PET studies of rats. Total/nonspecific binding at 60 min postinjection was 5.6 for (S)-[C- 11]CGP 12388 and 2.0 for the.(S)-F-18 compound. Due to its facile synt hetic procedure and in vivo data, (S)-[C-11]CGP 12388 is a promising b eta-adrenoceptor ligand for clinical PET.