Objective <p>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.</p> Methods <p>Wistar rats received doxorubicin (DOX; 2&#xa0;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.</p> Results <p>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.</p> Conclusion <p>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.</p>