0969-8051(94)00144-8 Nucl. Med. Biol. Vol. 22, No. 5, 617423, 1995 pp. Copyright 0 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0969-8051/95 $9.50 + 0.00 Synthesis and Characterization of [‘251]N-(2-aminoethyl)-4-iodobenzamide as a Selective Monoamine Oxidase B Inhibitor HAMID RAFII’,*, SYLVIE CHALON’, JEAN-EDOUARD OMBETTA3, YVES FRANGIN’, LUCETTE GARREAU’, ANNE-MARIE DOGNON’, ISABELLE LENA’, SYLVIE BODARD’, MARIE-PAULE VILAR’, JEAN-CLAUDE BESNARD’ and DENIS GUILLOTEAU’* ‘INSERM U316, Laboratoire de Biophysique Medicale et Pharmaceutique, UFR des Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France, 2Atomic Energy Organization of Iran, Nuclear Research Centre, P.O. Box 113658486. Tehran, Iran and 3Laboratoire de Chimie Organique Thirapeutique, UFR des Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France (Accepted 30 November 1994) We described the radiosynthesis of an analog of Ro 16-6491, [‘251]N-(2-aminoethyl)-4-iodobenzamide, for SPECT exploration of the monoamine oxidase B (MAO-B) in human brain. The radiolabelline: was carried out by nucleophilic exchange of the brominated precursor at solid-state phase in presence of ammonium sulphate. The radiochemical purity of radioiodinated product was higher than 95%. In comparison with Ro 16-6491, the in vitro studies showed a good selectivity of stable N-(2-aminoethyl)-4-iodobenzamide for MAO-B but a slightly lower affinity. Biodistribution studies in the rat showed a high and selective uptake of this compound in the pineal gland 1 h after i.v. injection. The cerebral uptake was low, but the coupling of [1251]N-(2-aminoethyl)-4-iodobenzamide with a lipophilic radical to enhance the passage through the blood-brain barrier can be envisaged. Introduction Monoamine oxidase [MAO, EC 1.4.3.41 is a flavin- containing enzyme which binds to outer mito- chondrial membrane. It catalyzes the oxidative deamination of various monoamines and plays an important role in the regulation of monoaminergic transmission in the central nervous system. This enzyme exists in two forms, namely MAO-A and MAO-B, which can be distinguished by their different sensitivities to inhibitors and their specificities for substrates. MAO-A oxidazes serotonin (5-HT) and is selectively inhibited by clorgyline whereas MAO-B oxidazes P-phenylethylamine (PEA) and is selectively inhibited by L-deprenyl (Knoll et al., 1972). Inhibitors of both forms of MAO have been shown to bc useful as therapeutic agents. Indeed an increase of MAO-B activity has been observed in some neuro- logical disorders such as Parkinson’s disease (Riederer and Jellinger, 1983), Alzheimer’s disease (Adolfsson et al., 1980) and Huntington’s chorea (Mann et al., 1986). At present MAO-B inhibitors are used for treatment of the Parkinson’s disease (Lewin, 1985; Strolin Benedetti and Dostert, 1989). It would *Author for correspondence. be therefore of great value to explore MAO-B activity in uiuo by scintigraphic method. Currently, suicide inhibitors of MAO-B such as L-deprenyl have been used as positron emitting ligands for PET studies, and permitted to map MAO-B in human brain (Fowler et al., 1987). Since this type of ligand binds irreversibly to the enzyme, a quantitative in vivo method with an equilibrium model cannot be used. Until now, no reversible ligand was used for the quantification of MAO-B with scintigraphic method. Ro 16-6491, N-(2-aminoethyl)-4-chlorobenzamide, is a non-toxic, reversible and short-acting MAO-B inhibitor with high selectivity (Kettler et al., 1985). Therefore, radioiodinated derivatives of this com- pound may be useful radioligands for in vivo selective localization and activity determination of MAO-B. Ohmomo et nl. (1992) reported the synthesis and some characterizations of iodinated derivatives of Ro 16-6491. They emphasized especially upon N-(2-aminoethyl)-2-chloro+iodobenzamide, and in vivo cerebral distribution of radiolabelled compounds was not reported. We choose to synthesize and to characterize an iodinated derivative of Ro 16-6491 in which the chloride atom was replaced by an iodide atom, the N-(2-aminoethyl)-4-iodobenzamide. Therefore, N-(2-aminoethyl)-4-bromobenzamide was 617