Preparation of [¹²³I]‐ and [¹²⁵I]epidepride: A dopamine D‐2 receptor antagonist radioligand

Abstract

Abstract ( S )‐(−)‐ N ‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐[ 123 I]iodo‐2,3‐dimethoxybenzamide (TDP 517) (proposed generic name, [ 123 I]epidepride) is the iodine‐123 substituted analogue of isoremoxipride (FLB 457), both of which are very potent dopamine D‐2 antagonists (epidepride K D 0.024 nM). [ 123 I]Epidepride was radioiodinated in 60–70% radiochemical yields in 35 min from the corresponding 5‐(tributyltin) derivative using Na 123 I with a specific radioactivity of 3000 Ci/mmol, and oxidized in situ with chloramine‐T. The aryltin precursor was prepared from non‐labelled epidepride by palladium‐catalyzed stannylation using bis(tri‐ n ‐butyltin) in triethylamine. Alternatively, using no carrier‐added Na 125 I as the radioisotope, [ 125 I]epidepride at 2000 Ci/mmol specific radioactivity was prepared in 86% radiochemical yield and 99% radiochemical purity after purification by reverse phase HPLC in ethanolic phosphate buffer.