A change of in vivo characteristics depending on specific activity of radioiodinated (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-pIV] as a ligand for sigma receptor imaging

The radioiodinated (+)-p-iodovesamicol [(+)-pIV], which shows a high binding affinity for sigma-1 (σ-1) receptors, is prepared by an exchange reaction. The specific activity (SA) is fairly low and therefore is insufficient for clinical use. In this study, we prepared (+)-[125I]pIV with a high SA from tributylstannyl precursor and compared the in vivo characteristics between high and low SA by imaging σ-1 receptors in the central nervous system. In the biodistribution study, a difference in brain accumulation was observed between the two methods. At 30 min postinjection, the brain accumulation (1.58%ID/g) of low SA [0.6–1.1 TBq/mmol (16–30 Ci/mmol)] (+)-[125I]pIV was higher than that (1.34%ID/g) of high SA [>88.8 TBq/mmol (>2400 Ci/mmol)] (+)-[125I]pIV. In the blocking study, the brain uptake of high SA (+)-[125I]pIV was reduced more significantly by the coadministration of sigma ligands such as pentazocine, haloperidol or SA4503 than that of low SA (+)-[125I]pIV. These results showed that nonspecific binding of high SA (+)-[125I]pIV in the brain was lower than that of low SA (+)-[125I]pIV, and high SA (+)-[125I]pIV bound more specifically to σ-1 receptors in the brain than low SA (+)-[125I]pIV. In contrast, in the blood-binding study, high SA (+)-[125I]pIV (58.4%) bound to blood cells with higher affinity than low SA (+)-[125I]pIV (46.0%). In metabolite studies, blood metabolites of high SA (+)-[125I]pIV (57.3±3.5%) were higher than those of low SA (+)-[125I]pIV (45.5±4.1%) at 30 min postinjection. Higher SA may be apt to bind to blood cells with higher affinity and to be metabolized faster.