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

Abstract

Abstract(S)‐(−)‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐[123I]iodo‐2,3‐dimethoxybenzamide (TDP 517) (proposed generic name, [123I]epidepride) is the iodine‐123 substituted analogue of isoremoxipride (FLB 457), both of which are very potent dopamine D‐2 antagonists (epidepride KD 0.024 nM). [123I]Epidepride was radioiodinated in 60–70% radiochemical yields in 35 min from the corresponding 5‐(tributyltin) derivative using Na123I 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 Na125I as the radioisotope, [125I]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.