Dynamic expression of the myocardial sigma-1 receptor after doxorubicin cardiomyopathy using radioiodine-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5 V) imaging

Abstract

Objective

We aimed to evaluate the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of doxorubicin-induced cardiotoxicity.

Methods

Wistar rats received doxorubicin (DOX; 2 mg/kg/week) as an intraperitoneal injection. Gated ^{99 m}Tc-MIBI SPECT was performed for cardiac function evaluation, and ^{99 m}Tc-DSMA scintigraphy was performed for renal function assessment. Various organs’ uptake (%ID/g) of ¹²⁵I-OI5V was estimated in the rats before and at three, five, and seven weeks after the injection.

Results

No rats died during DOX injections, until eight weeks. The left ventricular cavity volume increased compared to before DOX injection at five weeks after DOX injection. At seven weeks post-DOX injection, the ejection fraction decreased compared with that before the injection. DMSA scintigraphy revealed that renal function decreased significantly after seven weeks. In the post-mortem tissue counting study, ¹²⁵I-OI5V uptake decreased from five weeks post-injection. After DOX injection, the tracer uptake in the kidney decreased and the tracer uptake in the blood increased.

Conclusion

The present study confirmed the expression pattern of σ1R expression after DOX injection. A decrease in σ1R expression detected using ¹²⁵I-OI5V may serve as an earlier marker of DOX-induced cardiotoxicity compared with ejection fraction decline.