Highly efficient synthesis of [11C]PE2I, a selective radioligand for the quantification of the dopamine transporter using PET

PE2I ((E)-N-(3-iodoprop-2-enyl)-2 beta-carbomethoxy-3 beta-(4'-tolyl) nortropane) is a cocaine derivative belonging to a new generation of selective dopamine transporter inhibitors. Labelled with iodine-123 (half-life : 13.1 hours), PE2I has been dedicated to the diagnostics of neurodegenerative diseases such as Parkinson's disease in humans using single photon emission computed tomography. Labelled with carbon-11 (half-life : 20.4 minutes), it can be used in the absolute quantification of the dopamine transporter (DAT) using the high-resolution, sensitive and non-invasive quantitative imaging technique PET (positron emission tomography). In this paper, the radiosynthesis of carbon-ii labelled PE2I was investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, 200 to 300 mCi (7.4-11.1 GBq) of [C-11]PE2I were routinely obtained within 25 minutes of radiosynthesis (including HPLC purification) with specific radioactivities ranging from 0.8 to 1.2 Ci/mu mol (29.6-44.4 GBq/mu mol). Based on the preliminary PET experiments, it can be assumed that this radioligand would permit quantification of the DAT using PET and mathematical compartmental ligand-transporter models.