Depending on Species Specificity Influence of Difference Metabolic Function in the Biodistribution of Radiolabeled Sigma Ligand as the Tumor Seeking Agent
Radioiodinated (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-pIV], a sigma ligand, has been reported to show high uptake in tumor. A weak point of radiolabeled (+)-pIV as a tumor seeking agent is high uptake in sigma receptor rich organs such as liver, lung and kidney in mouse. However, recently, we investigated the liver uptake of (+)-[I-125]pIV was low in rat. So, biodistribuiton and metabolism studies of (+)-[I-125]pIV were performed into mouse and rat to investigate the relation between these functions.
(+)-[I-125]pIV was prepared from (+)-p-tributylstannyl-vesamicol by iododestannylation reaction under no-carrier-added conditions. (+)-[I-125]pIV was administrated IV into mice and rats and organs were collected, weighed and counted to investigate the biodistribution. Plasma and tissue extracts were analyzed by TLC.
(+)-[I-125]pIV showed high uptake in liver, lung and kidney in mice. Mouse liver uptake increased at 6hr postinjection. On the contrary, (+)-[I-125]pIV showed high uptake in only lung in rats. Sigma receptor rich rat organs showed decrease radioactivity from 30min postinjection. (+)-[I-125]pIV showed more prolonged presence of non-metabolized (+)-[I-125]pIV in mouse than in rat organs. (+)-[I-125]pIV was metabolized to four and two metabolites in mouse and rat, respectively. Low liver uptake in rat was contributed by water soluble metabolite and high uptake in mice liver was due to more hydrophobic metabolites.
Sigma rich organs uptake of (+)-[I-125]pIV such as radiolabeled sigma ligands depended on metabolic function in animals. In evaluation of radiolabeled receptor ligand as a tumor seeking agent, metabolic function of animals may be considered. Now, we are investigating metabolite in tumor.