一项多机构研究，调查小鼠全脑电子闪烁术后的疏松效应：功能、电生理和神经源终点的可重复性和时间演变。

IF 4.9 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2024-09-16 DOI:10.1016/j.radonc.2024.110534

Olivia G.G. Drayson , Stavros Melemenidis , Nikita Katila , Vignesh Viswanathan , Enikö A. Kramár , Richard Zhang , Rachel Kim , Ning Ru , Benoit Petit , Suparna Dutt , Rakesh Manjappa , M. Ramish Ashraf , Brianna Lau , Luis Soto , Lawrie Skinner , Amu S. Yu , Murat Surucu , Peter G. Maxim , Paola Zebadua-Ballasteros , Marcelo A. Wood , Charles L. Limoli

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引用次数: 0

摘要

背景和目的：超高剂量率放疗（FLASH）已被证明可减轻与常规剂量率放疗（CONV）相关的正常组织毒性，同时不影响临床前模型中的肿瘤杀伤效果。临床前放射研究（包括 FLASH）的一个突出挑战是在多个机构间验证物理剂量测定和生物效应：我们曾在不同的机构使用标准化的模型和剂量计证明了两种不同的电子 FLASH 设备的剂量测定可重复性。在本研究中，两家机构都对无肿瘤的成年雌性小鼠进行了 10 Gy 全脑 FLASH 和 CONV 照射，并对多个神经生物学终点的可重复性和时间演变进行了评估：结果：FLASH对新物体识别（辐照后 4 个月）和电生理长期潜能（LTP，辐照后 5 个月）行为表现的影响在两家机构之间是相同的。FLASH和CONV在海马神经发生（Sox2、双皮质素）、神经炎症（小胶质细胞活化）和电生理学（LTP）终点方面的差异在早期（48小时至2周）没有观察到，但FLASH在3周前对未成熟神经元的恢复更大：总之，我们在两个不同的机构，通过有效的剂量测定，证明了两种不同光束对大脑的FLASH疏导效果具有可重复性。FLASH对评估终点的疏导作用在较晚的时间点而不是最早的时间点表现出来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints

查看原文本刊更多论文

Background and Purpose

Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions.

Materials and Methods

We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints.

Results

FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH.

Conclusion

In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.

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来源期刊

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.