Radioiodinated analogs of xylamine: N‐(2‐chloroethyl)‐N‐ethyl‐2‐[125I]iodobenzylamine and N,N‐diethyl‐2‐[125I]iodobenzylamine as potential tools for monoamine uptake exploration by spect

Abstract

AbstractIn order to improve the scintigraphy and radiotherapy of neuroendocrine tumors we synthesized two radioiodinated benzylamines [N‐(2‐chloroethyl)‐N‐ethyl‐2‐[125I]iodobenzylamine and N,N‐diethyl‐2‐[125I]iodobenzylamine], analogs of xylamine [N‐(2‐chloroethyl)‐N‐ethyl‐2‐methylbenzylamine]. Xylamine is an irreversible inhibitor of uptake and accumulation of noradrenaline. The two unlabelled iodinated derivatives [N‐(2‐chloroethyl)‐N‐ethyl‐2‐iodobenzylamine and N,N‐diethyl‐2‐iodobenzylamine] were synthesized, purified and checked by HPLC, NMR and mass spectrography. Their affinity for the noradrenaline transporter was determined in vitro on rat brain membrane homogenates with [3H]nisoxetine. Radioiodination was performed by iodide for bromide nucleophilic exchange from brominated precursors. The N,N‐diethyl‐2‐[125I]iodobenzylamine was obtained directly from N,N‐diethyl‐2‐bromobenzylamine. Radiosynthesis of N‐(2‐chloroethyl)‐N‐ethyl‐2‐[125I]iodobenzylamine required three steps. A new brominated precursor [N‐ethyl‐N‐(2‐bromobenzyl)glycine ethyl ester] which was stable for radiolabelling and suitable for reduction to N‐(2‐hydroxyethyl)‐N‐cthyl‐2‐[125I]iodobenzylamine was synthesized. N‐(2‐Hydroxyethyl)‐N‐ethyl‐2‐[125I]iodobenzylamine was converted to N‐(2‐chloroethyl)‐N‐ethyl‐2‐[125I]iodobenzylamine in the presence of an excess of thionyl chloride. Radioiodinated derivatives were purified and checked by HPLC.