Preparation of [¹⁸F]β-CFT-FP and [¹¹C]β-CFT-FP, selective radioligands for visualisation of the dopamine transporter using Positron Emission Tomography (PET)

In this study the N-fluoropropyl analogue of the cocaine congener β-CFT (I), N-(3fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane (β-CFT-FP, III), was labelled with ¹⁸F or ¹¹C. Syntheses of the precursors nor-β-CFT (II) and β-CFT-FP acid (IV) as well as III itself are described. [ ¹⁸F]β-CFT-FP was prepared starting from I using two different labelling reagents [ ¹⁸F]fluoropropyl bromide (V) and [ ¹⁸F]fluoropropyl tosylate (VI). A reversed-phase HPLC system proved to be effective in separating the labelled product from precursor II. The radiochemical incorporation of V or VI to yield [ ¹⁸F]β-CFT-FP ( ¹⁸F-III) was in general 30-50% and the radiochemical purity was higher than 99%. [ ¹¹C]βCFT-FP ( ¹¹C-III) was synthesised by esterification of IV using [ ¹¹C]methyl triflate (VII). An HPLC-purification system using a reversed-phase column proved to be effective in separating the product from the acid precursor. The radiochemical yield starting from [ ¹¹C]carbon dioxide was 30-40% and the radiochemical purity was better than 99%. ¹⁸F-III and ¹¹C-III have potential as radioligands for visualisation of the dopamine transporter (DAT) using Positron Emission Tomography (PET).