¹²⁵I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (¹²⁵I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia

We aimed to explore how the severity of myocardial ischemia affects myocardial sigma-1 receptor (Sig-1R) expression using ¹²⁵I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (¹²⁵I-OI5V) imaging.

The left coronary artery was occluded for 30, 20, and 10 minute, to vary the severity of myocardial ischemia, followed by reperfusion. Dual-tracer autoradiography of the left ventricular short-axis slices was performed 3 and 7 days after reperfusion. ¹²⁵I-OI5V was injected 30 minute before sacrifice and the area at risk (AAR) was evaluated by ^99mTc-MIBI. Intense ¹²⁵I-OI5V uptake was observed in the AAR and was significantly increased with increasing ischemia duration. To evaluate salvaged and nonsalvaged areas (preserved and decreased perfusion areas), triple-tracer autoradiography was performed 3 days after reperfusion. After dual-tracer autoradiography, ²⁰¹Tl was injected 20 minute post ¹²⁵I-OI5V injection. On triple-tracer autoradiography, the AAR/normally perfused area ¹²⁵I-OI5V uptake ratio was positively correlated with the nonsalvaged area/whole left ventricular (LV) area ratio (P < .05). The AAR/normally perfused area ¹²⁵I-OI5V uptake ratio was negatively correlated with the ²⁰¹Tl uptake ratio of the AAR to normally perfused areas (P < .05). The comparison of the immunostaining distribution of ¹²⁵I-OI5V and the macrophage marker CD68 revealed that ¹²⁵I-OI5V was present mainly in, and immediately adjacent to the macrophage infiltration area.

Significant ¹²⁵I-OI5V uptake in the AAR depends on the duration of ischemia and reduced ²⁰¹Tl uptake; furthermore, ¹²⁵I-OI5V was found in and around the macrophage infiltrate area. These results indicate that iodine-labeled OI5V is a promising tool for visualizing Sig-1R expression according to the ischemic burden.