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Synthesis and in vivo evaluation of 3‐[ 11 C]methyl‐(3‐methoxy‐naphthalen)‐2‐yl‐(1‐benzyl‐piperidin)‐4‐yl‐acetate (SB‐235753), as a putative dopamine D 4 receptors antagonist for PET
Author(s) -
Matarrese M.,
Soloviev D.,
Moresco R. M.,
Todde S.,
Simonelli P.,
Colombo D.,
Magni F.,
Carpinelli A.,
Fazio F.,
Kienle M. Galli
Publication year - 2000
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/(sici)1099-1344(20000330)43:4<359::aid-jlcr323>3.0.co;2-v
Subject(s) - chemistry , radiosynthesis , radioligand , in vivo , biodistribution , desmethyl , hydrochloride , receptor , radiochemistry , in vitro , biochemistry , metabolite , microbiology and biotechnology , biology
(3‐Methoxy‐naphthalen)2‐yl‐(1‐benzyl‐piperidin)4‐yl‐acetate (SB‐235753) was labelled with 11 C (t 1/2 =20·4 min) as a putative radioligand for the non‐invasive assessment of Dopamine D 4 receptors in vivo with positron emission tomography (PET). The precursor for the radiosynthesis 3‐hydroxynaphthyl‐2‐[N‐benzyl)‐piperidyl]‐acetate hydrochloride was prepared by a four‐step synthesis starting from ethyl‐4‐pyridyl acetate. The radiolabelling consisted of methylation with [ 11 C]methyltriflate in dimethylformamide in the presence of potassium hydroxide. [ 11 C]SB‐235753, was synthesised in 30 min with a radiochemical yield of 10±5% (EOS, non‐decay corrected) with 99% radiochemical purity and specific radioactivity of 10±3 Ci/μmol. Biodistribution studies in rats with [ 11 C]SB‐235753 showed the uniform distribution of the tracer within different areas of the murine brain. At 30 min after injection 99% of the radioligand in plasma and 100% in cerebellum was metabolised. These findings suggest that [ 11 C]SB‐235753 can not be a suitable tracer for dopamine D 4 receptor studies with PET. Copyright © 2000 John Wiley & Sons, Ltd.