Chen Zhuoqing, Wakabayashi Hiroshi, Mori Hiroshi, Hiromasa Tomo, Zhang Xue, Kozaka Takashi, Ogawa Kazuma, Kinuya Seigo, Taki Junichi
Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan.
Division of Probe Chemistry for Disease Analysis, Research Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, Japan.
Ann Nucl Med. 2025 May 29. doi: 10.1007/s12149-025-02062-3.
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.
Wistar rats received doxorubicin (DOX; 2 mg/kg/week) as an intraperitoneal injection. Gated Tc-MIBI SPECT was performed for cardiac function evaluation, and Tc-DSMA scintigraphy was performed for renal function assessment. Various organs' uptake (%ID/g) of I-OI5V was estimated in the rats before and at three, five, and seven weeks after the injection.
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, I-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.
The present study confirmed the expression pattern of σ1R expression after DOX injection. A decrease in σ1R expression detected using I-OI5V may serve as an earlier marker of DOX-induced cardiotoxicity compared with ejection fraction decline.
我们旨在评估放射性标记的2-[4-(2-碘苯基)哌啶基]环戊醇（OI5V）在阿霉素诱导的心脏毒性大鼠模型中所显示的σ1受体（σ1R）强度和分布的表达情况。
Wistar大鼠腹腔注射阿霉素（DOX；2mg/kg/周）。进行门控Tc-MIBI单光子发射计算机断层扫描以评估心脏功能，进行Tc-DSMA闪烁扫描以评估肾功能。在注射前以及注射后3周、5周和7周对大鼠体内I-OI5V在各器官的摄取量（%ID/g）进行估算。
在阿霉素注射期间直至8周均无大鼠死亡。阿霉素注射后5周，左心室腔容积相较于注射前增大。阿霉素注射后7周，射血分数相较于注射前降低。二巯基丁二酸闪烁扫描显示7周后肾功能显著下降。在尸检组织计数研究中，I-OI5V摄取量自注射后5周开始下降。阿霉素注射后，肾脏中的示踪剂摄取量降低，血液中的示踪剂摄取量增加。
本研究证实了阿霉素注射后σ1R的表达模式。与射血分数下降相比，使用I-OI5V检测到的σ1R表达降低可能是阿霉素诱导的心脏毒性的早期标志物。
