Particle Beam Radiobiology Status and Challenges: A PTCOG Radiobiology Subcommittee Report.

Particle therapy (PT) represents a significant advancement in cancer treatment, precisely targeting tumor cells while sparing surrounding healthy tissues thanks to the unique depth-dose profiles of the charged particles. Furthermore, their linear energy transfer and relative biological effectiveness enhance their capability to treat radioresistant tumors, including hypoxic ones. Over the years, extensive research has paved the way for PT's clinical application, and current efforts aim to refine its efficacy and precision, minimizing the toxicities.

Cancer radioresistance is characterized by a differential lipid droplet content along the cell cycle.

Background: Cancer radiation treatments have seen substantial advancements, yet the biomolecular mechanisms underlying cancer cell radioresistance continue to elude full understanding. The effectiveness of radiation on cancer is hindered by various factors, such as oxygen concentrations within tumors, cells' ability to repair DNA damage and metabolic changes. Moreover, the initial and radiation-induced cell cycle profiles can significantly influence radiotherapy responses as radiation sensitivity fluctuates across different cell cycle stages.

Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

Purpose: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom.

Methods And Materials: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.

The DRESDEN PLATFORM is a research hub for ultra-high dose rate radiobiology.

The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research.

Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional audit of dosimetric variability between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene ($~1.

Radio-resistance of hypoxic tumors: exploring the effects of oxygen and x-ray radiation on non-small lung cancer cell lines.

Background: Solid tumors are often riddled with hypoxic areas, which develops as a result of high proliferation. Cancer cells willingly adapt and thrive in hypoxia by activating complex changes which contributes to survival and enhanced resistance to treatments, such as photon radiation. Photon radiation primarily relies on oxygen for the production of reactive oxygen species to induce DNA damage.

Development and characterization of a versatile mini-beam collimator for pre-clinical photon beam irradiation.

Background: Interest in spatial fractionation radiotherapy has exponentially increased over the last decade as a significant reduction of healthy tissue toxicity was observed by mini-beam irradiation. Published studies, however, mostly use rigid mini-beam collimators dedicated to their exact experimental arrangement such that changing the setup or testing new mini-beam collimator configurations becomes challenging and expensive.

Purpose: In this work, a versatile, low-cost mini-beam collimator was designed and manufactured for pre-clinical applications with X-ray beams.

Changes in Radical Levels as a Cause for the FLASH effect: Impact of beam structure parameters at ultra-high dose rates on oxygen depletion in water.

The influence of different average and bunch dose rates in electron beams on the FLASH effect was investigated. The present study measures O content in water at different beam pulse patterns and finds strong correlation with biological data, strengthening the hypothesis of radical-related mechanisms as a reason for the FLASH effect.

Beam pulse structure and dose rate as determinants for the flash effect observed in zebrafish embryo.

Background And Purpose: Continuing recent experiments at the research electron accelerator ELBE at the Helmholtz-Zentrum Dresden-Rossendorf the influence of beam pulse structure on the Flash effect was investigated.

Materials And Methods: The proton beam pulse structure of an isochronous cyclotron (UHDR) and a synchrocyclotron (UHDR) was mimicked at ELBE by quasi-continuous electron bunches at 13 MHz delivering mean dose rates of 287 Gy/s and 177 Gy/s and bunch dose rates of 10Gy/s and 10 Gy/s, respectively. For UHDR, 40 ms macro pulses at a frequency of 25 Hz superimposed the bunch delivery.

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance.

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma, and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of lipid droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1).

A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level.

Whilst the impact of hypoxia and ionizing radiations on gene expression is well-understood, the interplay of these two effects is not. To better investigate this aspect at the gene level human bladder, brain, lung and prostate cancer cell lines were irradiated with photons (6 Gy, 6 MV LINAC) in hypoxic and normoxic conditions and prepared for the whole genome analysis at 72 h post-irradiation. The analysis was performed on the obtained 20,000 genes per cell line using PCA and hierarchical cluster algorithms to extract the most dominant genes altered by radiation and hypoxia.

Does FLASH deplete oxygen? Experimental evaluation for photons, protons, and carbon ions.

Purpose: To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons, and carbon ions.

Methods: This study presents measurements of the oxygen consumption in sealed, 3D-printed water phantoms during irradiation with x-rays, protons, and carbon ions at varying dose rates up to 340 Gy/s. The oxygen measurement was performed using an optical sensor allowing for noninvasive measurements.

Iron and copper complexes with antioxidant activity as inhibitors of the metastatic potential of glioma cells.

Gliomas are the most common type of primary brain tumors, presenting high mortality and recurrence rates that highlight the need for the development of more efficient therapies. In that context, we investigated iron(iii) (FeL) and copper(ii) (CuL) complexes containing the tetradentate ligand 2-{[(3-chloro-2-hydroxy-propyl)-pyridin-2-ylmethyl-amino]-methyl}-phenol (L) as potential antimetastatic compounds in glioma cells. These complexes were designed to act as mimetics of antioxidant metalloenzymes (catalases and superoxide dismutase) and thus interfere with the production of reactive oxygen species (ROS), important signaling molecules that have been linked to the induction of Epithelial-Mesenchymal Transition (EMT) in cancer cells, a process associated with cancer invasion and aggressiveness.

Evaluation of Additional Track Parameters from Fluorescent Nuclear Track Detectors to Determine the LET of Individual Ions.

The measurement of single-track intensity in fluorescence nuclear track detectors can yield relative linear energy transfer (LET)-spectra with small line-width. The absolute determination of LET is, however, currently hampered by the inter-detector variability of crystal coloration and hence detector sensitivity. We therefore investigated the LET response of three additional quantities (average width and the variation of intensity and width along single tracks) using detectors irradiated with mono-energetic ion beams with LETs from 1.