High-throughput, low-cost FLASH: irradiation of Drosophila melanogaster with low-energy X-rays using time structures spanning conventional and ultrahigh dose rates.

Abstract

FLASH radiotherapy is an emerging technique in radiation oncology that may improve clinical outcomes by reducing normal tissue toxicities. The physical radiation characteristics needed to induce the radiobiological benefits of FLASH are still an active area of investigation. To determine the dose rate, range of doses and delivery time structure necessary to trigger the FLASH effect, Drosophila melanogaster were exposed to ultrahigh dose rate (UHDR) or conventional radiotherapy dose rate (CONV) 120-kVp X-rays. A conventional X-ray tube outfitted with a shutter system was used to deliver 17- to 44-Gy doses to third-instar D. melanogaster larvae at both UHDR (210Gy/s) and CONV (0.2-0.4Gy/s) dose rates. The larvae were then tracked through development to adulthood and scored for eclosion and lifespan. Larvae exposed to UHDR eclosed at higher rates and had longer median survival as adults compared to those treated with CONV at the same doses. Eclosion rates at 24Gy were 68% higher for the UHDR group (P<0.05). Median survival from 22Gy was >22days for UHDR and 17days for CONV (P<0.01). Two normal tissue-sparing effects were observed for D. melanogaster irradiated with UHDR 120-kVp X-rays. The effects appeared only at intermediate doses and may be useful in establishing the dose range over which the benefits of FLASH can be obtained. This work also demonstrates the usefulness of a high-throughput fruit fly model and a low-cost X-ray tube system for radiobiological FLASH research.