9.4 T static magnetic field ameliorates imatinib mesylate-induced toxicity and depression in mice

Purpose 9.4 T magnetic resonance imaging (MRI) has been initially tested on healthy human volunteers, but its future application will benefit more from experiments with animal disease models. In the meantime, high static magnetic fields (SMFs) have been shown to improve mice mental health and have anti-tumor potentials. Methods We compared the anti-tumor effects of 9.4 T SMF with or without a commonly used chemotherapy drug imatinib mesylate on BALB/c (Nu/Nu) mice bearing gastrointestinal stromal tumor GIST-T1 cells. The body weight, food/water consumption, complete blood count, blood biochemistry, tumor weight, HE and Ki67 stains were examined. Locomotor activity and cognitive functions were also measured by four behavior tests, including open field, elevated plus maze, three-chamber and tail suspension tests. Results We found that the tumor growth was inhibited up to 62.88% when treated with 9.4 T SMF alone for 200 h. More importantly, 9.4 T SMF combined with 20 mg/kg imatinib mesylate can result in 92.75% tumor suppression, which is close to the anti-tumor effect of high dose (80 mg/kg) imatinib. However, 80 mg/kg imatinib caused severe side effects, including significantly reduced gain of body weight, abnormal liver function and depressive behaviors in mice. In contrast, 9.4 T SMF treatment significantly reduced these side effects, especially for the depressive behaviors. Conclusion Our results demonstrate that 9.4 T SMF not only has anti-tumor effects on its own, but also could improve the anti-tumor effect of imatinib mesylate, reduce its toxicity and improve the mice mental health, which unraveled the great clinical potentials of high SMF in future applications.

目的：9.4T磁共振成像（MRI）最初已在健康人类志愿者身上进行了测试，但其未来应用将更多地受益于动物疾病模型实验。同时，高静磁场（SMFs）已被证明可改善小鼠心理健康并具有抗肿瘤潜力。 方法：我们比较了9.4T静磁场在有或无常用化疗药物甲磺酸伊马替尼的情况下对携带胃肠道间质瘤GIST - T1细胞的BALB/c（Nu/Nu）小鼠的抗肿瘤效果。检测了体重、食物/水摄入量、全血细胞计数、血液生化指标、肿瘤重量、HE和Ki67染色。还通过四种行为测试（包括旷场试验、高架十字迷宫试验、三室试验和悬尾试验）测量了运动活动和认知功能。 结果：我们发现，单独使用9.4T静磁场处理200小时，肿瘤生长抑制率可达62.88%。更重要的是，9.4T静磁场联合20mg/kg甲磺酸伊马替尼可使肿瘤抑制率达到92.75%，这接近于高剂量（80mg/kg）伊马替尼的抗肿瘤效果。然而，80mg/kg伊马替尼导致了严重的副作用，包括小鼠体重增加显著减少、肝功能异常和抑郁行为。相比之下，9.4T静磁场治疗显著减轻了这些副作用，尤其是抑郁行为。 结论：我们的结果表明，9.4T静磁场不仅自身具有抗肿瘤作用，还可提高甲磺酸伊马替尼的抗肿瘤效果，降低其毒性并改善小鼠心理健康，这揭示了高静磁场在未来应用中的巨大临床潜力。