Preparation of 8-[3-(4-fluorobenzoyl)-propyl]-1-(4-[123I] iodobenzoyl)-1,3,8-triazaspiro[4,5]decan-4-one: a novel selective serotonin 5-HT2 receptor agent.

In our attempt to develop radioiodinated serotonin 5-HT2 receptor imaging agents for routine clinical application with single photon emission computed tomography (SPECT), the [123I]iodinated compound 8-[3-(4-fluorobenzoyl)-propyl]1-(4-[123I]iodobenzoyl)- 1,3,8-triazaspiro[4,5]decan-4-one [123I]IBSP was prepared via no-carrier-added Cu(I)-assisted radio-iododebromination in acetic acid, followed by purification by means of reversed-phase HPLC in 70-90% radiochemical yield and high specific activities at a total synthesis time of 50 min. Moreover, [123I]-IBSP is stable up to 48 h in aqueous solution at room temperature and revealed appropriate lipophilicity (logP = 2.8) for good diffusion through the blood-brain-barrier. Competitive binding studies on rat brain membranes using [3H]ketanserin, [3H]SCH23390, and [3H]spiperone as radioligands (for 5-HT2, D1 and D2 receptors, respectively) indicated that IBSP has high affinity and selectivity for the serotonin 5-HT2 receptor (Ki = 7.0 nM) over the dopamine D2 (Ki = 153 nM) and D1 receptors (Ki = 265 nM). These data suggest that [123I]-IBSP may be a promising compound for studying 5-HT2 receptors with SPECT.