Speaker: Arthur F Petusseau, Postdoctoral researcher
Arthur F Petusseau: Hi, my name is Arthur Petusseau, I'm a postdoc at Dartmouth College at the Thayer School of Engineering, and in our recently published article in the Red Journal, we introduce a new approach using a fluorescent probe to measure oxygen depletion inside of the cells during ultra-high dose radiotherapy, or FLASH radiotherapy. In the past couple years, many groups have demonstrated the FLASH healthy tissue sparing effect and one of the hypotheses behind this FLASH effect is the oxygen depletion hypothesis. This hypothesis states that there is a significant oxygen depletion during FLASH, which doesn't have the same extent during conventional radiotherapy, and this is what leads to a radioprotection during FLASH of the healthy tissue. So, in this work, as I said, we use a fluorescent probe, Protoporphyrin IX, to measure oxygen inside the cells and the interesting aspect about using PpIX is that PpIX is an endogenous molecule that is synthesized as part of the heme synthesis pathway by the mitochondria within the cells. So, using this probe to measure oxygen allows to measure oxygen directly at the DNA damage site. And so here we measured oxygen depletion during different photon beams, radiations, and different doses: 10, 22, and 28 Gy. We demonstrated that these oxygen depletions are highly dependent on initial oxygen levels in a tissue before irradiation, and we measured average oxygen depletion per Gy of 0.56 millimeters of mercury inside of the cells and 0.43 millimeters of mercury outside of the cell in the interstitial space. So, to summarize, this new approach is novel in the fact that it measures oxygen depletion during FLASH inside of the cells. Extracellular measurements have been done the past couple years, so here, the novelty is in the fact that we measure oxygen at the DNA level during FLASH, and one of the very appealing effects of this approach is that the fluorescent probe that we use, Protoporphyrin IX, is an endogenously produced probe that is very well- tolerated by the organism, even in humans, and that is approved by the Food and Drug Administration in the US and approved in Europe as well. And so, this probe could potentially be used in humans to measure intracellular oxygen depletion during FLASH in upcoming clinical trials. So, please go read our article if you're interested and if you want more details. Thank you.
