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Synthesis and in vitro evaluation of 18 F‐labelled di‐ and tri(ethylene glycol) metomidate esters
Author(s) -
Erlandsson Maria,
Hall Håkan,
Långström Bengt
Publication year - 2009
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1597
Subject(s) - chemistry , imidazole , carboxylate , ethylene glycol , metabolite , alkyl , medicinal chemistry , ethylene , stereochemistry , organic chemistry , biochemistry , catalysis
By replacing the alkyl chain in a metomidate ester with 18 F‐labelled di‐ or tri(ethylene glycol) chains, two 18 F‐labelled PET tracers, i.e. 2‐(2‐[ 18 F]fluoroethoxy)ethyl 1‐[(1 R )‐1‐phenylethyl]‐1 H ‐imidazole‐5‐carboxylate (1) and 2‐[2‐(2‐[ 18 F]fluoroethoxy)ethoxy]ethyl 1‐[(1 R )‐1‐phenylethyl]‐1 H ‐imidazole‐5‐carboxylate (2), were synthesized. Two precursors, 2‐(2‐bromoethoxy)ethyl 1‐[(1 R )‐1‐phenylethyl]‐1 H ‐imidazole‐5‐carboxylate and 2‐[2‐(2‐chloroethoxy)ethoxy]ethyl 1‐[(1 R )‐1‐phenylethyl]‐1 H ‐imidazole‐5‐carboxylate, were prepared and used in one‐step nucleophilic [ 18 F]fluorination reactions using conventional and microwave heating. Organ distribution, frozen section autoradiography and metabolite analysis were performed. The decay‐corrected radiochemical yields of 1 and 2 were 26±8 and 23±8%, respectively, when they were prepared using conventional heating. By performing microwave heating, the reaction time could be decreased and the yields of analogues 1 and 2 could be increased to 57±12 and 51±18%, respectively. Organ distribution studies in the rat showed considerable uptake in the lungs, adrenals and liver. Both compounds bound with low nonspecific binding (1: approx. 20–30%; 2: 2.9% or lower) to tissue from pig and human normal and pathologic adrenals. Metabolite analyses were performed in rats after 5 and 30 min for tracer 1 (20±6 and 2±1%) and tracer 2 (27±5 and 6±4%). Both compounds are interesting candidates for the detection of different types of adrenal disorders. Copyright © 2009 John Wiley & Sons, Ltd.