Evaluation of the binding characteristics of [¹⁸F]fluoroproxyfan in the rat brain for in vivo visualization of histamine H₃ receptor

Histamine H₃ receptors play an important role in biological functions. The aim of this research was to examine whether histamine H₃ receptors can be visualized in vivo and in vitro with [¹⁸F]3-(1H-imidazol-4-yl)propyl 4-fluorobenzyl ether (fluoroproxyfan). [¹⁸F]Fluoroproxyfan was synthesized with high specific activity using [¹⁸F]benzyl bromide. The binding of [¹⁸F]fluoroproxyfan to rat brain homogenates was higher in the striatum and thalamus and was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [¹⁸F]fluoroproxyfan to the H₃ receptor in the rat brain. In accordance with the in vitro bindings, the in vivo distribution of [¹⁸F]fluoroproxyfan was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of large amounts of fluoroproxyfan. These data suggest that [¹⁸F]fluoroproxyfan can be potentially useful to image histamine H₃ receptor noninvasively in the human brain by positron emission tomography.