1 Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari, Iran .
2 Student Research Committee, Mazandaran University of Medical Sciences , Sari, Iran .
Cancer Biother Radiopharm. 2018 Nov;33(9):403-410. doi: 10.1089/cbr.2018.2523. Epub 2018 Jul 24.
Doxorubicin (DOX), despite having antitumor properties, also exhibits cardiotoxicity. Resveratrol has antitumor property for breast cancer cells. Tc-MIBI has higher absorption rate in human breast cancer cell line MCF-7. In the present study, the authors intend to investigate the effect of DOX and resveratrol on the absorption of Tc-MIBI in breast cancer cell xenografts in mice.
Sixteen xenograft models in nude mice were divided into four groups. Group I (S, control) received 2% DMSO in 0.9% saline, group II (D) 2.5 mg/kg DOX, group III (D + R) 20 mg/kg/d resveratrol with 2.5 mg/kg DOX (total dose of 15 mg/kg in six injections), and group IV (R) 20 mg/kg/d resveratrol for 2 weeks. Single-photon emission computed tomography (SPECT) images were taken for the determination of Tc-MIBI absorption. Mice were sacrificed, and the percentage of injected dose per gram (%ID/g) of the heart, liver, tumor, and muscle was measured using a gamma counter. Hematoxylin-eosin staining and Masson's trichrome staining were used for investigation of histopathological changes.
The %ID/g of tumor was lowest in group D + R. The severity of tumor necrosis or apoptosis was highest in group D + R, but there is no significant difference in pathological injuries and %ID/g of tumor between the group D + R and group D. In addition to the results of the %ID/g, the severity of pathological injuries to the liver and heart cells in group D + R was higher compared with group D. There is a significant difference in the %ID/g of the liver between the group D + R and group D. SPECT images showed that the lowest amount of %ID/g was observed in the tumor of group D + R.
According to the results of pathology, biodistribution study, and imaging, the combination of DOX and resveratrol has shown higher antitumor effect; hence, Tc-MIBI can be used to evaluate their antitumor effect.
多柔比星（DOX）虽具有抗肿瘤特性，但也具有心脏毒性。白藜芦醇具有抗肿瘤特性，可用于乳腺癌细胞。Tc-MIBI 在人乳腺癌细胞系 MCF-7 中的吸收率更高。在本研究中，作者旨在研究 DOX 和白藜芦醇对荷瘤小鼠乳腺癌细胞 Tc-MIBI 吸收的影响。
16 只荷瘤裸鼠模型分为 4 组。第 I 组（S，对照组）给予 0.9%生理盐水 2%二甲基亚砜（DMSO），第 II 组（D）给予 2.5mg/kg DOX，第 III 组（D+R）给予 DOX 2.5mg/kg/d 联合白藜芦醇 20mg/kg/d（总剂量为 15mg/kg，共 6 次注射），第 IV 组（R）给予白藜芦醇 20mg/kg/d 共 2 周。采用单光子发射计算机断层扫描（SPECT）测定 Tc-MIBI 吸收。采用γ计数器测量心脏、肝脏、肿瘤和肌肉的每克注射剂量百分比（%ID/g）。采用苏木精-伊红（HE）染色和 Masson 三色染色观察组织病理学变化。
D+R 组肿瘤的 %ID/g 最低。D+R 组肿瘤坏死或凋亡程度最高，但 D+R 组与 D 组肿瘤的病理损伤和 %ID/g 无显著差异。除了 %ID/g 的结果外，D+R 组肝脏和心肌细胞的病理损伤严重程度也高于 D 组。D+R 组与 D 组肝脏的 %ID/g 有显著差异。SPECT 图像显示，D+R 组肿瘤的 %ID/g 最低。
根据病理、生物分布研究和影像学结果，DOX 和白藜芦醇联合应用具有更高的抗肿瘤作用；因此，Tc-MIBI 可用于评估其抗肿瘤作用。
