Abstract
1043
Introduction: Sigma-1 receptor imaging probes for determining the expression level will be useful for diagnoses of various diseases and companion diagnosis of therapeutic agents targeting the sigma-1 receptor. In this study, our aim is developing better probes for sigma-1 receptor imaging. We synthesized aza-vesamicol homologous, in which alkyl chains of varying chain lengths were introduced between a piperazine ring and a benzene ring. The binding affinity for the sigma-1 receptor of the vesamicol derivatives tended to increase depending on the length of the alkyl chain between the benzene ring and the piperazine ring. The binding affinity for the sigma-1 receptorof 2-(4-(3-phenylpropyl)piperazin-1-yl)cyclohexan-1-ol (Ki= 5.8 nM) was the highest. Therefore, we introduced radioiodine into the benzene ring in this compound with 75% radiochemical yield and 98% radiochemical purity after purification by RP-HPLC. The radioiodine labeled probe, [125I]2-(4-(3-(4-iodophenyl)propyl)piperazin-1-yl)cyclohexan-1-ol,showed high accumulation in the sigma-1 receptor expressed DU-145 both in vitro (0.73 %dose/µg protein) and in vivo (6.27 %dose/g) at 1 h incubation and postinjection, respectively. Co-injection of this 125Iprobe with excess amount of haloperidol as sigma receptor ligand significantly decreased in the tumor accumulation in vitroand in vivo, indicating sigma receptor-mediated tumor uptake. These results give useful information for developing sigma-1 receptor imaging probes.