In Vitro And In Vivo Evaluation Of [I-125/123]-2-[4-(2-Iodophenyl)Piperidino]Cyclopentanol([I-125/123]-Oi5v ) As A Potential Sigma-1 Receptor Ligand For Spect

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 (sigma-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, sigma-1 and sigma-2 receptor by in vitro competitive binding assays using rat tissues and radioligands, [H-3]vesamicol, (+)-[H-3]pentazocine and [H-3]DTG, respectively. [I-125/123]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [I-125]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 [I-125]OI5V for sigma-1 receptor. SPECT-CT imaging study was performed using [I-123]OI5V.Results OI5V demonstrated high selective binding affinity for sigma-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [I-125]OI5V was high and the accumulation of [I-125]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [I-125]OI5V in the brain was significantly blocked by co-administration of 0.5 mu mol of SA4503 and 1.0 mu mol of pentazocine. Ex vivo autoradiography revealed that the regional brain accumulation of [I-125]OI5V was similar to sigma-1R-rich regions of the rat brain. SPECT images of [I-123]OI5V in the rat brain reflected the distribution of sigma receptors in the brain.Conclusions This study confirmed that [I-125/123]OI5V selectively binds sigma-1R in the rat brain in vivo. [I-123]OI5V was suggested to be useful as a sigma-1R ligand for SPECT.