Search Results (30)

In this study, we describe the preparation of carbon dots (CDs) from natural charcoal by laser ablation in a liquid. A continuum wave (CW) laser diode operating at a wavelength of 450 nm, hitting a solid carbon target placed into a biocompatible liquid, constituted of a phosphate-buffered saline (PBS) solution and distilled water, was used for the generation of the CDs suspension. Exploring the practical applications of carbon dots, it was observed that the luminescence of the produced CDs can be used as bioimaging in living organisms, environmental monitoring, chemical analysis, targeted drug delivery, disease diagnosis, therapy, and others. The CDs’ luminescence can be induced by UV irradiation and, as demonstrated in this study, by energetic MeV proton beams. The fluorescence was revealed mainly at 480 nm when UV illuminated the CDs, and also in the region at 514–642 nm when the CDs were irradiated by energetic proton ions. Atomic force microscopy (AFM) of the CD films revealed their spherical shape with a size of about 10 nm. The significance of the manuscript lies in the use of CDs produced by laser ablation exhibiting luminescence under irradiation of an energetic proton beam. Full article

Radiotherapy is one of the main cancer treatments being used for ~50% of all cancer patients. Conventional radiotherapy typically utilises X-rays (photons); however, there is increasing use of particle beam therapy (PBT), such as protons and carbon ions. This is because PBT elicits significant benefits through more precise dose delivery to the cancer than X-rays, but also due to the increases in linear energy transfer (LET) that lead to more enhanced biological effectiveness. Despite the radiotherapy type, the introduction of DNA damage ultimately drives the therapeutic response through stimulating cancer cell death. To combat this, cells harbour cell cycle checkpoints that enables time for efficient DNA damage repair. Interestingly, cancer cells frequently have mutations in key genes such as TP53 and ATM that drive the G₁/S checkpoint, whereas the G₂/M checkpoint driven through ATR, Chk1 and Wee1 remains intact. Therefore, targeting the G₂/M checkpoint through specific inhibitors is considered an important strategy for enhancing the efficacy of radiotherapy. In this review, we focus on inhibitors of Chk1 and Wee1 kinases and present the current biological evidence supporting their utility as radiosensitisers with different radiotherapy modalities, as well as clinical trials that have and are investigating their potential for cancer patient benefit. Full article

Recent experimental investigations have demonstrated that a substantial amount of H⁻/D⁻ ions can be formed by thermal desorption processes. Based on these new findings, new mini axial and coaxial-type neutron tubes have been developed for the production of high or low-energy neutrons via the d-d, d-¹⁰B, d-⁷Li or p-⁷Li nuclear reactions. By operating these mini neutron tubes with a high frequency AC high-voltage supply, short pulses of high intensity neutron beams can be generated. Multiple applications, such as carbon and well logging, neutron imaging, cancer therapy, medical isotope production, fission reactor start-up, fusion reactor material evaluation, homeland security and space exploration can be performed with the subcompact neutron generator system. It is shown that the performance of these new mini neutron tubes can exceed those of the conventional plasma-based neutron sources. Full article

Carbon ion beams have the unique property of higher linear energy transfer, which causes clustered damage of DNA, impacting the cell repair system. This sometimes triggers apoptosis and the release in the cytoplasm of damaged DNA, leading to type I interferon (IFN) secretion via the activation of the cyclic GMP–AMP synthase-stimulator of interferon genes pathway. Dendritic cells phagocytize dead cancer cells and damaged DNA derived from injured cancer cells, which together activate dendritic cells to present cancer-derived antigens to antigen-specific T cells in the lymph nodes. Thus, carbon ion radiation therapy (CIRT) activates anti-cancer immunity. However, cancer is protected by the tumor microenvironment (TME), which consists of pro-cancerous immune cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The TME is too robust to be destroyed by the CIRT-mediated anti-cancer immunity. Various modalities targeting regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages have been developed. Preclinical studies have shown that CIRT-mediated anti-cancer immunity exerts its effects in the presence of these modalities. In this review article, we provide an overview of CIRT-mediated anti-cancer immunity, with a particular focus on recently identified means of targeting the TME. Full article

Background: Multidisciplinary management is crucial in cancer diagnosis and treatment. Multidisciplinary teams include specialists in surgery, medical therapies, and radiation therapy (RT), each playing unique roles in oncology care. One significant aspect is RT, guided by radiation oncologists (ROs). This paper serves as a detailed primer for non-oncologists, medical students, or non-clinical investigators, educating them on contemporary RT practices. Methods: This report follows the process of RT planning and execution. Starting from the decision-making in multidisciplinary teams to the completion of RT and subsequent patient follow-up, it aims to offer non-oncologists an understanding of the RO’s work in a comprehensive manner. Results: The first step in RT is a planning session that includes obtaining a CT scan of the area to be treated, known as the CT simulation. The patients are imaged in the exact position in which they will receive treatment. The second step, which is the primary source of uncertainty, involves the delineation of treatment targets and organs at risk (OAR). The objective is to ensure precise irradiation of the target volume while sparing the OARs as much as possible. Various radiation modalities, such as external beam therapy with electrons, photons, or particles (including protons and carbon ions), as well as brachytherapy, are utilized. Within these modalities, several techniques, such as three-dimensional conformal RT, intensity-modulated RT, volumetric modulated arc therapy, scattering beam proton therapy, and intensity-modulated proton therapy, are employed to achieve optimal treatment outcomes. The RT plan development is an iterative process involving medical physicists, dosimetrists, and ROs. The complexity and time required vary, ranging from an hour to a week. Once approved, RT begins, with image-guided RT being standard practice for patient alignment. The RO manages acute toxicities during treatment and prepares a summary upon completion. There is a considerable variance in practices, with some ROs offering lifelong follow-up and managing potential late effects of treatment. Conclusions: Comprehension of RT clinical effects by non-oncologists providers significantly elevates long-term patient care quality. Hence, educating non-oncologists enhances care for RT patients, underlining this report’s importance. Full article

Helium ion beam therapy, one of the particle therapies developed and studied in the 1950s for cancer treatment, resulted in clinical trials starting at Lawrence Berkeley National Laboratory in 1975. While proton and carbon ion therapies have been implemented in research institutions and hospitals globally after the end of the trials, progress in comprehending the physical, biological, and clinical findings of helium ion beam therapy has been limited, particularly due to its limited accessibility. Ongoing efforts aim to establish programs that evaluate the use of helium ion beams for clinical and research purposes, especially in the treatment of sensitive clinical cases. Additionally, helium ions have superior physical properties to proton beams, such as lower lateral scattering and larger LET. Moreover, they exhibit similar physical characteristics to carbon, oxygen, and neon ions, which are all used in heavy ion therapy. However, they demonstrate a sharper lateral penumbra with a lower radiobiological absence of certainties and lack the degradation of variations in dose distributions caused by excessive fragmenting of heavier-ion beams, especially at greater depths of penetration. In this context, the status and the prospective advancements of helium ion therapy are examined by investigating ionization, recoil, and lateral scattering values using MC TRIM algorithms in mandible plate phantoms designed from both tissue and previously studied biomaterials, providing an overview for dental cancer treatment. An average difference of 1.9% in the Bragg peak positions and 0.211 mm in lateral scattering was observed in both phantoms. Therefore, it is suggested that the ⁴He ion beam can be used in the treatment of mandibular tumors, and experimental research is recommended using the proposed biomaterial mandible plate phantom. Full article

Particle minibeam therapy has demonstrated the potential for better healthy tissue sparing due to spatial fractionation of the delivered dose. Especially for heavy ions, the spatial fractionation could enhance the already favorable differential biological effectiveness at the target and the entrance region. Moreover, spatial fractionation could even be a viable option for bringing ions heavier than carbon back into patient application. To understand the effect of minibeam therapy, however, requires careful conduction of pre-clinical experiments, for which precise knowledge of the minibeam characteristics is crucial. This work introduces the use of high-spatial-resolution CMOS sensors to characterize collimator-produced carbon ion minibeams in terms of lateral fluence distribution, secondary fragments, track-averaged linear energy transfer distribution, and collimator alignment. Additional simulations were performed to further analyze the parameter space of the carbon ion minibeams in terms of beam characteristics, collimator positioning, and collimator manufacturing accuracy. Finally, a new concept for reducing the neutron dose to the patient by means of an additional neutron shield added to the collimator setup is proposed and validated in simulation. The carbon ion minibeam collimator characterized in this work is used in ongoing pre-clinical experiments on heavy ion minibeam therapy at the GSI. Full article

Motion compensation strategies in particle therapy depend on the anatomy, motion amplitude and underlying beam delivery technology. This retrospective study on pancreas patients with small moving tumours analysed existing treatment concepts and serves as a basis for future treatment strategies for patients with larger motion amplitudes as well as the transition towards carbon ion treatments. The dose distributions of 17 hypofractionated proton treatment plans were analysed using 4D dose tracking (4DDT). The recalculation of clinical treatment plans employing robust optimisation for mitigating different organ fillings was performed on phased-based 4D computed tomography (4DCT) data considering the accelerator (pulsed scanned pencil beams delivered by a synchrotron) and the breathing-time structure. The analysis confirmed the robustness of the included treatment plans concerning the interplay of beam and organ motion. The median deterioration of D_50% (ΔD_50%) for the clinical target volume (CTV) and the planning target volume (PTV) was below 2%, while the only outlier was observed for ΔD_98% with −35.1%. The average gamma pass rate over all treatment plans (2%/ 2 mm) was 88.8% ± 8.3, while treatment plans for motion amplitudes larger than 1 mm performed worse. For organs at risk (OARs), the median ΔD_2% was below 3%, but for single patients, essential changes, e.g., up to 160% for the stomach were observed. The hypofractionated proton treatment for pancreas patients based on robust treatment plan optimisation and 2 to 4 horizontal and vertical beams showed to be robust against intra-fractional movements up to 3.7 mm. It could be demonstrated that the patient’s orientation did not influence the motion sensitivity. The identified outliers showed the need for continuous 4DDT calculations in clinical practice to identify patient cases with more significant deviations. Full article

Purpose: This study evaluates beam angles used to generate highly individualized proton therapy treatment plans for patients eligible for carbon ion radiotherapy (CIRT). Methods and Materials: We retrospectively evaluated patients treated with pencil beam scanning intensity modulated proton therapy from 2015 to 2020 who had indications for CIRT. Patients were treated with a 190° rotating gantry with a robotic patient positioning system. Treatment plans were individualized to provide maximal prescription dose delivery to the tumor target volume while sparing organs at risk. The utilized beam angles were grouped, and anatomic sites with at least 10 different beam angles were sorted into histograms. Results: A total of 467 patients with 484 plans and 1196 unique beam angles were evaluated and characterized by anatomic treatment site and the number of beam angles utilized. The most common beam angles used were 0° and 180°. A wide range of beam angles were used in treating almost all anatomic sites. Only esophageal cancers had a predominantly unimodal grouping of beam angles. Pancreas cancers showed a modest grouping of beam angles. Conclusions: The wide distribution of beam angles used to treat CIRT-eligible patients suggests that a rotating gantry is optimal to provide highly individualized beam arrangements. Full article

LIDAL (Light Ion Detector for ALTEA, Anomalous Long-Term Effects on Astronauts) is a radiation detector designed to measure the flux, the energy spectra and, for the first time, the time-of-flight of ions in a space habitat. It features a combination of striped silicon sensors for the measurement of deposited energy (using the ALTEA device, which operated from 2006 to 2012 in the International Space Station) and fast scintillators for the time-of-flight measurement. LIDAL was tested and calibrated using the proton beam line at TIFPA (Trento Institute for Fundamental Physics Application) and the carbon beam line at CNAO (National Center for Oncology Hadron-therapy) in 2019. The performance of the time-of-flight system featured a time resolution (sigma) less than 100 ps. Here, we describe the detector and the results of these tests, providing ground calibration curves along with the methodology established for processing the detector’s data. LIDAL was uploaded in the International Space Station in November 2019 and it has been operative in the Columbus module since January 2020. Full article

Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine. Full article

Radiotherapy (ionising radiation; IR) is utilised in the treatment of ~50% of all human cancers, and where the therapeutic effect is largely achieved through DNA damage induction. In particular, complex DNA damage (CDD) containing two or more lesions within one to two helical turns of the DNA is a signature of IR and contributes significantly to the cell killing effects due to the difficult nature of its repair by the cellular DNA repair machinery. The levels and complexity of CDD increase with increasing ionisation density (linear energy transfer, LET) of the IR, such that photon (X-ray) radiotherapy is deemed low-LET whereas some particle ions (such as carbon ions) are high-LET radiotherapy. Despite this knowledge, there are challenges in the detection and quantitative measurement of IR-induced CDD in cells and tissues. Furthermore, there are biological uncertainties with the specific DNA repair proteins and pathways, including components of DNA single and double strand break mechanisms, that are engaged in CDD repair, which very much depends on the radiation type and associated LET. However, there are promising signs that advancements are being made in these areas and which will enhance our understanding of the cellular response to CDD induced by IR. There is also evidence that targeting CDD repair, particularly through inhibitors against selected DNA repair enzymes, can exacerbate the impact of higher LET, which could be explored further in a translational context. Full article

Particle therapy is a well established clinical treatment of tumors. More than one hundred particle therapy centers are in operation world-wide. The advantage of using hadrons like protons or carbon ions as particles for tumor irradiation is the distinct peak in the depth-dependent energy deposition, which can be exploited to accurately deposit doses in the tumor cells. To guarantee this, high accuracy in monitoring and control of the particle beam is of the utmost importance. Before the particle beam enters the patient, it traverses a monitoring system which has to give fast feedback to the beam control system on position and dose rate of the beam while minimally interacting with the beam. The multi-wire chambers mostly used as beam position monitors have their limitations when a fast response time is required (drift time). Future developments such as MRI-guided ion beam therapy pose additional challenges for the beam monitoring system, such as tolerance of magnetic fields and acoustic noise (vibrations). Solid-state detectors promise to overcome these limitations and the higher resolution they offer can create additional benefits. This article presents the evaluation of an HV-CMOS detector for beam monitoring, provides results from feasibility studies in a therapeutic beam, and summarizes the concepts towards the final large-scale assembly and readout system. Full article

Proton (p) and carbon (C) ion beams are in clinical use for cancer treatment, although other particles such as He, Be, and B ions have more recently gained attention. Identification of the most optimal ion beam for radiotherapy is a challenging task involving, among others, radiobiological characterization of a beam, which is depth-, energy-, and cell type- dependent. This study uses the FLUKA and MCDS Monte Carlo codes in order to estimate the relative biological effectiveness (RBE) for several ions of potential clinical interest such as p, ⁴He, ⁷Li, ¹⁰Be, ¹⁰B, and ¹²C forming a spread-out Bragg peak (SOBP). More specifically, an energy spectrum of the projectiles corresponding to a 5-cm SOBP at a depth of 8 cm was used. All secondary particles produced by the projectiles were considered and RBE was determined based on radiation-induced Double Strand Breaks (DSBs), as calculated by MCDS. In an attempt to identify the most optimal ion beam, using the latter data, biological optimization was performed and the obtained depth–dose distributions were inter-compared. The results showed that ¹²C ions are more effective inside the SOBP region, which comes at the expense of higher dose values at the tail (i.e., after the SOBP). In contrast, p beams exhibit a higher $D_{SOPB}/D_{Entrance}$ ratio, if physical doses are considered. By performing a biological optimization in order to obtain a homogeneous biological dose (i.e., dose × RBE) in the SOBP, the corresponding advantages of p and ¹²C ions are moderated. ⁷Li ions conveniently combine a considerably lower dose tail and a $D_{SOPB}/D_{Entrance}$ ratio similar to ¹²C. This work contributes towards identification of the most optimal ion beam for cancer therapy. The overall results of this work suggest that ⁷Li ions are of potential interest, although more studies are needed to demonstrate the relevant advantages. Future work will focus on studying more complex beam configurations. Full article

This work presents the tests of a multi-gap detector (MGD), composed of three parallel-plate ionization chambers (ICs) with different gap widths, assembled to prove the capability of correcting for charge volume recombination which is expected to occur when high fluence rates are delivered. Such beam conditions occur with a compact accelerator for charged particle therapy developed to reduce the costs, to accomplish faster treatments and to exploit different beam delivery techniques and dose rates as needed, for example, for range modulation and FLASH irradiations, respectively. The MGD was tested with carbon ions at the Centro Nazionale di Adroterapia Oncologica (CNAO Pavia, Italy), and with protons in two different beam lines: at Bern University Hospital with continuous beams and at the Laboratori Nazionale del Sud (Catania, Italy) of the Italian National Center of Nuclear Physics (INFN) with pulsed beams. For each accelerator, we took measurements with different beam intensities (up to the maximum rate of ionization achievable) and changed the detector bias voltage (V) in order to study the charge collection efficiency. Charge recombination models were used to evaluate the expected collected charge and to measure the linearity of the rate of ionization with the beam fluence rate. A phenomenological approach was used to determine the collection efficiency (f₁) of the chamber with thinnest gap from the relative efficiencies, f₁/f₂ and f₁/f₃, exploiting the condition that, for each measurement, the three chambers were exposed to the same rate of ionization. Results prove that two calibration curves can be determined and used to correct the online measurements for the charge losses in the ICs for recombination. Full article