title: Synthesis and preliminary evaluation of (R,S)-1-[2-((carbamoyl-4-hydroxy)phenoxy)-ethylamino]-3-[4-(1-[11C]-met hyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol ([11C]CGP 20712A) as a selective beta 1-adrenoceptor ligand for PET.
abstract: The most selective beta 1-adrenoceptor ligand known at this moment is (S)-1-[2-((carbamoyl-4-hydroxy) phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl) phenoxy]-2-propanol (CGP 26505), the S-isomer of CGP 20712A. We prepared the racemic 11C analogue by methylation with [11C]CH3I of the corresponding desmethyl compound using a microwave oven to accelerate the reaction. Several radioactive by-products (about 70% of the non-volatile radioactive products) were formed. After HPLC purification [11C]CGP 20712A with a specific activity of 35 TBq/mmol was dissolved in a propylene glycol-ethanol-saline mixture to prepare it for injection. The total preparation time was 35 min. The radiochemical yield was 5% (calculated from [11C]CH3I, not corrected for decay). The identity of [11C]CGP 20712A was proved by liquid chromatography-mass spectrometry (LC-MS). Tissue distribution studies in male Wistar rats have been performed. At 20 min after injection of the radioligand (0.1 nmol) the DAR [differential absorption ratio = (counts per minute recovered/g tissue)/(counts per min injected/g body weight)] in heart tissue decreased significantly (P < 0.005) from 1.84 +/- 0.11 to 1.21 +/- 0.12 after blocking of beta-adrenoceptors with 500 micrograms (R,S)-propranolol. A preliminary PET study in a Wistar rat showed maximal uptake in the time frame 10-20 min after injection. The ratio of specific/non-specific binding at this interval was 2.6.
authors.affiliation: PET Center and Groningen Center for Catalysis and Synthesis, University Hospital, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: A
authors.initials: A
authors.lastname: Van Waarde
authors.forename: G M
authors.initials: GM
authors.lastname: Visser
authors.forename: W
authors.initials: W
authors.lastname: Vaalburg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D005069:Evaluation Studies as Topic; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000502:physiology; D014055:Tomography, Emission-Computed
chemical_list: D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D007093:Imidazoles; C049763:CGP 20712A