Synthesis and in vivo evaluation of 3-[11C]methyl-(3-methoxy-naphthalen)-2-yl-(1-benzyl-piperidin)-4-yl-acetate (SB-235753), as a putative dopamine D4 receptors antagonist for PET

Article abstract of DOI:10.1002/(SICI)1099-1344(20000330)43:4<359::AID-JLCR323>3.0.CO;2-V

(3-Methoxy-naphthalen)-2-yl-(1-benzyl-piperidin)-4-yl-acetate (SB-235753) was labelled with ¹¹C (t(1/2) = 20.4 min) as a putative radioligand for the non-invasive assessment of Dopamine D₄ 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 [¹¹C]methyltriflate in dimethylformamide in the presence of potassium hydroxide. [¹¹C]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 [¹¹C]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 [¹¹C]SB-235753 can not be a suitable tracer for dopamine D₄ receptor studies with PET.