Neuroprotective Effects of Ultra-High Dose Rate FLASH Bragg Peak Proton Irradiation

被引：39

作者：

Dokic, Ivana ^{[1
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]}

Meister, Sarah ^{[1
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]}

Bojcevski, Jovana ^{[1
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,7
]}

Tessonnier, Thomas ^{[7
]}

Walsh, Dietrich ^{[1
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]}

Knoll, Maximilian ^{[1
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]}

Mein, Stewart ^{[1
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]}

Tang, Zili ^{[1
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]}

Vogelbacher, Lena ^{[1
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Rittmueller, Claudia ^{[1
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]}

Moustafa, Mahmoud ^{[1
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]}

Krunic, Damir ^{[10
]}

Brons, Stephan ^{[7
]}

Haberer, Thomas ^{[7
]}

Debus, Juergen ^{[1
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,7
]}

Mairani, Andrea ^{[7
,11
]}

Abdollahi, Amir ^{[1
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,7
]}

机构：

[1] Heidelberg Univ Hosp UKHD, Natl Ctr Tumor Dis NCT, Clin Cooperat Unit Translat Radiat Oncol, Heidelberg, Germany

[2] German Canc Res Ctr, Heidelberg, Germany

[3] Heidelberg Fac Med MFHD, Dept Radiat Oncol, Div Mol & Translat Radiat Oncol, Heidelberg, Germany

[4] Heidelberg Univ Hosp UKHD, Heidelberg Ion Beam Therapy Ctr HIT, Heidelberg, Germany

[5] German Canc Res Ctr, German Canc Consortium DKTK Core Ctr Heidelberg, Heidelberg, Germany

[6] Heidelberg Univ, Natl Ctr Radiat Oncol NCRO, Heidelberg Inst Radiat Oncol HIRO, Heidelberg, Germany

[7] Heidelberg Ion Beam Therapy Ctr HIT, Heidelberg, Germany

[8] Heidelberg Univ, Fac Biosci, Heidelberg, Germany

[9] Suez Canal Univ, Dept Clin Pathol, Ismailia, Egypt

[10] German Canc Res Ctr, Light Microscopy Facil, Heidelberg, Germany

[11] Natl Ctr Ontol Hadrontherapy CNAO, Pavia, Italy

来源：

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2022年 / 113卷 / 03期

关键词：

HMGB1; RADIATION; THERAPY; CELLS; NEUROINFLAMMATION; INFLAMMATION; MICROGLIA; MEDIATOR; RELEASE;

D O I：

10.1016/j.ijrobp.2022.02.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: To investigate brain tissue response to ultra-high dose rate (uHDR, FLASH) and standard dose rate (SDR) proton irradiations in the Bragg peak region. Methods and Materials: Active scanning uHDR delivery was established for proton beams for investigation of dose rate effects between clinical SDR and uHDR at similar to 10 Gy in the Bragg peak region (dose-averaged linear energy transfer [LETD] ranging from 4.5 to 10.2 keV mu m(-1)). Radiation- induced injury of neuronal tissue was assessed by studying the DNA double strand break repair kinetics surrogated by nuclear gamma H2AX staining (radiation induced foci [RIF]), microvascular density and structural integrity (MVD, CD31+ endothelium), and inflammatory microenvironmental response (CD68+ microglia/macrophages and high mobility group box protein 1[HMGB]) in healthy C57BL/6 mouse brains. Results: Averaged dose rates achieved were 0.17 Gy/s (SDR) and 120 Gy/s (uHDR). The fraction of RIF-positive cells increased after SDR similar to 10-fold, whereas a significantly lower fraction of RIF-positive cells was found after uHDR versus SDR (similar to 2 fold, P <.0001). Moreover, uHDR substantially preserved the microvascular architecture and reduced microglia/macrophage regulated associated inflammation as compared with SDR. Conclusions: The feasibility of uHDR raster scanning proton irradiation is demonstrated to elicit FLASH sparing neuroprotective effects compared to SDR in a preclinical in vivo model. (C) 2022 The Authors. Published by Elsevier Inc.

引用

页码：614 / 623

页数：10

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