PREPARATION OF 123]IODOBENZOYL)-1,3,8-TRIAZASPIRO[4,5]DECAN-4-ONE - ANOVEL SELECTIVE SEROTONIN 5-HT2 RECEPTOR AGENT

In our attempt to develop radioiodinated serotonin 5 HT2 receptor imag ing agents for routine clinical application with single photon emissio n computed tomography (SPECT), the [I-123]iodinated compound 123]iodob enzoyl)-1,3,8-triazaspiro[4,5]decan-4-one [I-123]IBSP was prepared via no carrier added Cu(I)-assisted radio-iododebromination in acetic aci d, 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, [I-123]-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. Compet itive binding studies on rat brain membranes using [H-3]ketanserin, [H -3]SCH23390, and [3H]spiperone as radioligands (for 5-HT2, D-1 and D-2 receptors, respectively) indicated that IBSP has high affinity and se lectivity for the serotonin 5-HT, receptor (K-i = 7.0 nM) over the dop amine D-2 (K-i = 153 nM) and D-1 receptors (K-i = 265 nM), These data suggest that [I-123]-IBSP may be a promising compound for studying 5-H T2 receptors with SPECT. (C) 1997 Elsevier Science Inc.