PMID: 8868289Feb 1, 1996Paper

(S,S)- and (S,R)-1'-[18F]fluorocarazolol, ligands for the visualization of pulmonary beta-adrenergic receptors with PET

Nuclear Medicine and Biology
P H ElsingaW Vaalburg

Abstract

The beta-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in the isopropyl group via a reductive alkylation by [18F]-fluoroacetone of the corresponding (S)-desisopropyl compound according to a known procedure. The introduction of fluorine in the isopropyl group creates a new stereogenic centre resulting in the formation of (S,S)- and (S,R)-1'-[18F]fluorocarazolol, which were separated by HPLC. Tissue distribution studies were performed in male Wistar rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mmol) showed high uptake in lung and heart, which could be blocked by pretreatment of the animals with (+/-)-propranolol. No significant differences were observed between the biodistribution of the two diastereomers. Metabolite analysis showed a rapid appearance of polar metabolites in plasma, while at 60 min postinjection 92% and 82% of the total radioactivity in lung and heart was unmetabolized 1'-[18F]fluorocarazolol. In a PET-study with male Wistar rats, the lungs were clearly visualized and the pulmonary uptake was decreased after pretreatment of the animals with (+/-)-propranolol. The heart could not be visualized. Similar results were obtained in PET-studies with lambs.

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Citations

Feb 24, 2001·Medical & Biological Engineering & Computing·R F MuzicM S Berridge
May 25, 2005·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·P H ElsingaWillem Vaalburg
May 7, 1998·European Journal of Pharmacology·A Van WaardeW Vaalburg
Aug 14, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·R F MuzicM S Berridge
Nov 28, 2002·Nuclear Medicine and Biology·H ValetteDaniel Marzin
Oct 1, 2003·Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T·P H ElsingaWillem Vaalburg

Related Concepts

Fluorocarazolol, (R-(R*, R*))-stereoisomer
Adrenergic beta-Antagonists
Metabolic Biotransformation
Brain
Carbazoles
Erythrocytes
Fluorine Radioisotopes
Isotope Labeling, Stable
Ligands
Lung

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