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

Article abstract of DOI:10.1002/jlcr.2580360711

In 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)-Nethyl-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-ethyl-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.