Synthesis and evaluation of (S)-4-(3-(2'-[C-11]isopropylamino)-2-hydroxy-propoxy)-2H-benzimidazol-2-one ((S)-[C-11]CGP 12388) and (S)-4-(3-((1'-[F-18]-fluoroisopropyl)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-butylamino)-2-hydroxypropoxy)- 2H-benzimidazol-2[C-11]-one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthesis of [C-11]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-C GP 12388 (4-(3-(isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one), 5, the isopropyl analogue of CGP 12177,has been labeled with carbon-11 in the isopropyl group via a reductive alkylation by [C-11]acetone (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 via 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 35 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). Biodistribution studies in rats demonstrated specific binding to beta-adrenoceptors 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 synthetic procedure and in vivo data, (S)-[C-11]CGP 12388 is a promising beta-adrenoceptor ligand for clinical PET.