Magnetic resonance biomarkers for timely diagnostic of radiation dose-rate effects

Diagnostic of radiation effects can be obtained within hours from delivery relying on spectroscopic detection of cell metabolite concentrations. Clinical and pre-clinical studies show that radiation delivery with elevated dose-rates can achieve tumor suppression while minimizing toxicity to surrounding areas. Diagnostic biomarkers detected on short timescales are needed to orient high dose-rate radiation delivery. We have designed an 1H magnetic resonance approach to observe metabolite concentrations, in particular Choline, Creatine, and Lactate, in order to detect radiation dose and dose-rate effects within hours from radiation delivery. The results of our metabolic profiling method in glioblastoma cells are consistent with observations from clinical studies guided by magnetic resonance spectroscopy for radiotherapy of head tumors. At 5 Gy/min we have observed increases in lactate concentrations and decreases in [Cho]/[Cr] ratios at increasing radiation doses. An increase of the radiation dose-rate to 35 Gy/min is correlated with an increase of [Cho]/[Cr] consistent with a reduction in radiation-induced oxidative effects at high dose-rates. The observed biomarkers can be translated for radiation pulse sequences optimization. One Sentence SummaryMagnetic resonance biomarkers to monitor biological effectiveness within hours after radiation delivery can be optimized for glioblastoma cells and are of potential use for the design of radiotherapy with high dose-rates.