title: Synthesis and evaluation of (S)-4-(3-(2'-[11C]isopropylamino)-2-hydroxypropoxy) -2H-benzimidazol -2-one ((S)-[11C]CGP 12388) and (S)-4-(3-((1'-[18F]-fluoroisopropyl)amino)-2-hydroxypropoxy) -2H- benzimidazol-2-one ((S)-[18F]fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emission tomography.
abstract: The beta-adrenoceptor antagonist (S)-[11C]CGP 12177 (4-(3-(tert-butylamino)-2-hydroxypropoxy)-2H-benzimidazol -2[11C]- one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthesis of [11C]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-CGP 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 [11C]acetone (3) of the corresponding (S)-desisopropyl compound 2. The fluoro-substituted analogue of (S)-CGP 12388 was prepared by reacting 2 with [18F]fluoroacetone (4). (S)-[11C]CGP 12388 (5) was easily prepared via a one-pot procedure. The radiochemical yield of (S)-[11C]CGP 12388 (600-800 Ci/mmol, EOS) was 18% (EOB) with a total synthesis time of 35 min, whereas (S)-[18F]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)-[18F]fluoro-CGP 12388 and (S)-[11C]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)-[11C]CGP 12388 and 2.0 for the (S)-18F compound. Due to its facile synthetic procedure and in vivo data, (S)-[11C]CGP 12388 is a promising beta-adrenoceptor ligand for clinical PET.
authors.affiliation: PET-center, University Hospital Groningen, The Netherlands. p.h.elsinga@pet.azg.nl
authors.forename: P H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: A
authors.initials: A
authors.lastname: van Waarde
authors.forename: K A
authors.initials: KA
authors.lastname: Jaeggi
authors.forename: G
authors.initials: G
authors.lastname: Schreiber
authors.forename: M
authors.initials: M
authors.lastname: Heldoorn
authors.forename: W
authors.initials: W
authors.lastname: Vaalburg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: C109240:4-(3-((1-fluoroprop-2-yl)amino)-2-hydroxypropoxy)-2H-benzimidazol-2-one; D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D011943:Receptors, Adrenergic, beta; C109239:CGP 12388