Laser‐driven radiation: Biomarkers for molecular imaging of high dose‐rate effects

Abstract

Recently developed short‐pulsed laser sources garner high dose‐rate beams such as energetic ions and electrons, x rays, and gamma rays. The biological effects of laser‐generated ion beams observed in recent studies are different from those triggered by radiation generated using classical accelerators or sources, and this difference can be used to develop new strategies for cancer radiotherapy. High‐power lasers can now deliver particles in doses of up to several Gy within nanoseconds. The fast interaction of laser‐generated particles with cells alters cell viability via distinct molecular pathways compared to traditional, prolonged radiation exposure. The emerging consensus of recent literature is that the differences are due to the timescales on which reactive molecules are generated and persist, in various forms. Suitable molecular markers have to be adopted to monitor radiation effects, addressing relevant endogenous molecules that are accessible for investigation by noninvasive procedures and enable translation to clinical imaging. High sensitivity has to be attained for imaging molecular biomarkers in cells and in vivo to follow radiation‐induced functional changes. Signal‐enhanced MRI biomarkers enriched with stable magnetic nuclear isotopes can be used to monitor radiation effects, as demonstrated recently by the use of dynamic nuclear polarization (DNP) for biomolecular observations in vivo. In this context, nanoparticles can also be used as radiation enhancers or biomarker carriers. The radiobiology‐relevant features of high dose‐rate secondary radiation generated using high‐power lasers and the importance of noninvasive biomarkers for real‐time monitoring the biological effects of radiation early on during radiation pulse sequences are discussed.

Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

“…A focus for future activities in this area across Europe will be at the facilities of the Extreme Light Infrastructure (ELI), particularly at ELI Beamlines (Czech Republic), where the Extreme Light Infrastructure Multidisciplinary Applications of Laser-Ion Acceleration (ELIMAIA) beam lines in Prague are being commissioned [44]. ELI Nuclear Physics (ELI NP) Romania, is also planning an involvement in laser-driven ion radiobiology research [45]. In the United Kingdom, the main facilities used for this research are located at the Central Laser Facility of the Rutherford Appleton Laboratory (RAL) (GEMINI and VULCAN lasers), the University of Strathclyde (SCAPA) and Queen's University Belfast (TARANIS), with activities in this area carried out so far within the EPSRC-funded A-SAIL consortium.…”

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

“…The initial radiation impact defines the time-scale beyond which cell radiation response is triggered. The response is reflected in the cellular metabolites [31], amongst which several biomarkers detected in this study are outlined.…”

Challenges and Advances in the Application of Dynamic Nuclear Polarization to Liquid-State NMR Spectroscopy

“…13 C-Labeled pyruvate is the most commonly used molecular probe in metabolic imaging, which is expected to be highly impactful as a clinical tool because of the non-invasive nature of magnetic resonance techniques and non-toxicity of spin probes, , many of which occur endogenously. Metabolic imaging of hyperpolarized pyruvate is expected to be useful for tracking the redox status of tissues, oxidative stress, and profiling the effects of radiation. − Similar to the study by Thaning et al, Ardenkjær-Larsen et al. demonstrated the use of metabolic imaging to scan implanted tumors in rats and to quantify the glycolytic status of cancer cells .…”