The role of radiation-induced bystander effects in radiation therapy remains unclear. With renewed interest in therapy with α-particle emitters, and their potential for sterilizing disseminated tumor cells (DTCs), it is critical to determine the contribution of bystander effects to the overall response so they can be leveraged for maximum clinical benefit. Methods: Female Foxn1nu athymic nude mice were administered 0, 50, or 600 kBq/kg 223RaCl2 to create bystander conditions. At 24 hours after administration, MDA-MB-231 or MCF-7 human breast cancer cells expressing luciferase were injected into the tibial marrow compartment. Tumor burden was tracked weekly via bioluminescence. Results: The MDA-MB-231 xenografts were observed to have a 10-day growth delay in the 600 kBq/kg treatment group only. In contrast, MCF-7 cells had 7- and 65-day growth delays in the 50 and 600 kBq/kg groups, respectively. Histologic imaging of the tibial marrow compartment, α-camera imaging, and Monte Carlo dosimetry modeling revealed DTCs both within and beyond the range of the α-particles emitted from 223Ra in bone for both MCF-7 and MDA-MB-231 cells. Conclusion: Taken together, these results support the participation of 223Ra-induced antiproliferative/cytotoxic bystander effects in delayed growth of DTC xenografts. They indicate that the delay depends on the injected activity and therefore is dose-dependent. They suggest using 223RaCl2 as an adjuvant treatment for select patients at early stages of breast cancer.

中文翻译：

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223Ra治疗的小鼠骨髓异种移植瘤的剂量依赖性生长延迟：旁观者效应的作用及其治疗潜力。

辐射引起的旁观者效应在放射治疗中的作用尚不清楚。随着人们对使用α粒子发射器的治疗方法重新产生兴趣，以及它们对已扩散的肿瘤细胞（DTC）进行消毒的潜力，确定旁观者效应对总体反应的贡献至关重要，以便可以利用它们来获得最大的临床收益。方法：给雌性Foxn1nu无胸腺裸鼠0、50或600 kBq / kg 223RaCl2，以建立旁观者​​条件。给药后24小时，将表达荧光素酶的MDA-MB-231或MCF-7人乳腺癌细胞注射到胫骨骨髓腔中。每周通过生物发光追踪肿瘤负担。结果：仅在600 kBq / kg治疗组中，观察到MDA-MB-231异种移植物有10天的生长延迟。相比之下，在50和600 kBq / kg组中，MCF-7细胞分别具有7天和65天的生长延迟。胫骨腔室的组织学成像，α照相机成像和蒙特卡洛剂量学模型揭示了MCF-7和MDA-MB-231细胞在骨骼中从223 Ra发射的α颗粒范围之内和之外的DTC。结论：综上所述，这些结果支持了223 Ra诱导的抗增殖/细胞毒性旁观者效应参与了DTC异种移植物的延迟生长。它们表明延迟取决于注射的活性，因此是剂量依赖性的。他们建议使用223RaCl2作为乳腺癌早期特定患者的辅助治疗。蒙特卡洛（Monte Carlo）剂量学模型揭示了MCF-7和MDA-MB-231细胞的DTC都在骨中从223 Ra发射的α粒子范围之内和之外。结论：综上所述，这些结果支持了223 Ra诱导的抗增殖/细胞毒性旁观者效应参与了DTC异种移植物的延迟生长。它们表明延迟取决于注射的活性，因此是剂量依赖性的。他们建议使用223RaCl2作为乳腺癌早期特定患者的辅助治疗。蒙特卡洛（Monte Carlo）剂量学模型揭示了MCF-7和MDA-MB-231细胞的DTC都在骨中从223 Ra发射的α粒子范围之内和之外。结论：综上所述，这些结果支持了223 Ra诱导的抗增殖/细胞毒性旁观者效应参与了DTC异种移植物的延迟生长。它们表明延迟取决于注射的活性，因此是剂量依赖性的。他们建议使用223RaCl2作为乳腺癌早期特定患者的辅助治疗。它们表明延迟取决于注射的活性，因此是剂量依赖性的。他们建议使用223RaCl2作为乳腺癌早期特定患者的辅助治疗。它们表明延迟取决于注射的活性，因此是剂量依赖性的。他们建议使用223RaCl2作为乳腺癌早期特定患者的辅助治疗。