Document Detail

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.
MedLine Citation:
PMID:  9234285     Owner:  NLM     Status:  MEDLINE    
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.
P H Elsinga; A Van Waarde; G M Visser; W Vaalburg
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  21     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1997-09-25     Completed Date:  1997-09-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  211-7     Citation Subset:  IM    
PET Center and Groningen Center for Catalysis and Synthesis, University Hospital, The Netherlands.
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MeSH Terms
Adrenergic beta-Antagonists / chemical synthesis*,  metabolism
Carbon Radioisotopes / diagnostic use
Evaluation Studies as Topic
Imidazoles / chemical synthesis*,  metabolism
Molecular Structure
Radioligand Assay
Rats, Wistar
Tissue Distribution / physiology
Tomography, Emission-Computed*
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Carbon Radioisotopes; 0/Imidazoles; 81015-67-0/CGP 20712A

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