Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice - PubMed (original) (raw)

. 2014 Jul 16;6(245):245ra93.

doi: 10.1126/scitranslmed.3008973.

Laura Caplier 2, Virginie Monceau 3, Frédéric Pouzoulet 4, Mano Sayarath 4, Charles Fouillade 4, Marie-France Poupon 4, Isabel Brito 5, Philippe Hupé 6, Jean Bourhis 7, Janet Hall 4, Jean-Jacques Fontaine 2, Marie-Catherine Vozenin 8

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Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

Vincent Favaudon et al. Sci Transl Med. 2014.

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Abstract

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

Copyright © 2014, American Association for the Advancement of Science.

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