In vitro and in vivo evaluation of [125/123I]-2-[4-(2-iodophenyl)piperidino]cyclopentanol([125/123I]-OI5V) as a potential sigma-1 receptor ligand for SPECT.

INTRODUCTION: We investigated the characteristics of radio-iodinated 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) as a single photon emission computed tomography (SPECT) ligand for mapping sigma-1 receptor (σ-1R), which plays an important role in stress remission in many organs. METHODS: OI5V was synthesized from o-bromobenzaldehyde in three steps. OI5V was evaluated for its affinity to VAChT, σ-1 and σ-2 receptor by in vitro competitive binding assays using rat tissues and radioligands, [3H]vesamicol, ( +)-[3H]pentazocine and [3H]DTG, respectively. [125/123I]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [125I]OI5V in blood, brain regions and major organs of rats was performed at 2, 10, 30 and 60 min post-injection. In vivo blocking study and ex vivo autoradiography were performed to assess the binding selectivity of [125I]OI5V for σ-1 receptor. SPECT-CT imaging study was performed using [123I]OI5V. RESULTS: OI5V demonstrated high selective binding affinity for σ-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [125I]OI5V was high and the accumulation of [125I]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [125I]OI5V in the brain was significantly blocked by co-administration of 0.5 µmol of SA4503 and 1.0 µmol of pentazocine. Ex vivo autoradiography revealed that the regional brain accumulation of [125I]OI5V was similar to σ-1R-rich regions of the rat brain. SPECT images of [123I]OI5V in the rat brain reflected the distribution of sigma receptors in the brain. CONCLUSIONS: This study confirmed that [125/123I]OI5V selectively binds σ-1R in the rat brain in vivo. [123I]OI5V was suggested to be useful as a σ-1R ligand for SPECT.