Abstract
In developing monoamine oxidase (MAO)-B specific radioligands, N-(2-aminoethyl)-2-chloro-4-[125I]iodobenzamide ([125I]FIBA) was conveniently synthesized from its tributylstannyl precursor by an iododestannylation reaction using sodium [125I]iodide and hydrogen peroxide with high radiochemical yield. The method should be applicable for labeling with 123I, a suitable radioisotope for in vivo imaging with single photon emission computed tomography (SPECT). In vitro binding studies using mouse brain mitochondrial preparations showed that the specific binding of [125I]FIBA was saturable and of high affinity. Calculated values for KD and Bmax were 201 nM and 9.5 pmol/mg protein, respectively. The [125I]FIBA binding was effectively prevented by MAO-B specific inhibitors (l-deprenyl, Ro 16-6491, FIBA) or substrate (β-phenethylamine). However, MAO-A specific inhibitor (clorgyline) and substrate (serotonin) had no significant effect. After an intravenous injection into mice, [125I]FIBA showed high brain uptake (1.64% dose/g at 15-30 min post injection) and long retention (1.11% dose/g at 120 min post injection) in the brain. Good brain-to-blood radioactivity ratios of 2.19 and 2.41 at 60 and 120 min after injection, respectively, were obtained. The in vitro binding data and in vivo characteristics suggested that [125I]FIBA is potentially useful as a probe for biological studies including specific labeling of MAO-B in vivo as well as in vitro. Moreover, the 123I-labeled counterpart, [123I]FIBA, might be valuable for non-invasive imaging and mapping of MAO-B in the living brain with SPECT.
