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Background: Radiation fields encountered in proton therapy (PT) and ionbeam therapy (IBT) are characterized by a variable linear energy transfer (LET), which lead to a variation of relative biological effectiveness and also affect the response of certain dosimeters. Therefore, reliable tools to measure LET are advantageous to predict and correct LET effects. Fluorescent nuclear track detectors (FNTDs) are suitable to measure LET spectra within the range of interest for PT and IBT, but so far the accuracy and precision have been challenged by sensitivity variations between individual crystals. Purpose: To develop a novel methodology to correct changes in the fluorescent intensity due to sensitivity variations among FNTDs. This methodology is based on exposing FNTDs to alpha particles in order to derive a detector-specific correction factor. This will allow us to improve the accuracy and precision of LET spectra measurements with FNTDs. Methods: FNTDs were exposed to alpha particles. Afterward, the detectors were irradiated to monoenergetic protons, 4He-, 12C-, and 16O-ions. At each step, the detectors were imaged with a confocal laser scanning microscope. The tracks were reconstructed and analyzed using in-house developed tools. Alpha-particle tracks were used to derive a detector-specific sensitivity correction factor (ks,i). Proton, 4He-, 12C-, and 16O-ion tracks were used to establish a traceable calibration curve that relates the fluorescence intensity with the LET in water (LETH2O). FNTDs from a second batch were exposed and analyzed following the same procedures, to test if ks,i can be used to extend the applicability of the calibration curve to detectors from different batches. Finally, a set of blind tests was performed to assess the accuracy of the proposed methodology without user bias. Throughout all stages, the main sources of uncertainty were evaluated. Results: Based on a sample of 100 FNTDs, our findings show a high sensitivity heterogeneity between FNTDs, with ks,i having values between 0.57 and 2.55. The fitting quality of the calibration curve, characterized by the mean absolute percentage residuals and correlation coefficient, was improved when ks,i was considered. Results for detectors from the second batch show that, if the fluorescence signal is corrected by ks,i,the differences in the predicted LETH2O with respect to the reference set are reduced from 55%, 141%, 41%, and 186% to 4.2%, 6.5%, 5.0%, and 11.0%,for protons, 4He-, 12C-, and 16O-ions, respectively. The blind tests showed that it is possible to measure the track- and doseaverage LETH2O with an accuracy of 0.3%, 16%, and 9.6% and 1.7%, 28%, and 30% for protons, 12C-ions and mixed beams, respectively. On average, the combined uncertainty of the measured LETH2O was 11%, 13%, 21%, and 26% for protons, 4He-, 12C-, and 16O-ions, respectively. These values were increased by a mean factor of 2.0 when ks,i was not applied. Conclusions: We have demonstrated for the first time that alpha particles can be used to derive a detector-specific sensitivity correction factor. The proposed methodology allows us to measure LET spectra using FNTD-technology, with a degree of accuracy and precision unreachable before with sole experimental approaches. [ABSTRACT FROM AUTHOR]

The synthesis of a new type of intrinsically chiral, directly [beta],[beta]'-linked, octa-meso-aryl-substituted bisporphyrins is described, by using an optimized Suzuki-Miyaura coupling procedure. The novel axially chiral bis(tetrapyrrole) compounds are potentially useful as substrates for asymmetric catalysis, biomimetic studies on directed electron-transfer processes, for photodynamic therapy (PDT), and for chiral recognition.

Background Purpose Methods Results Conclusions In‐vivo monitoring methods of carbon ion radiotherapy (CIRT) includes explorations of nuclear reaction products generated by carbon‐ion beams interacting with patient tissues. Our research group focuses on in‐vivo monitoring of CIRT using silicon pixel detectors. Currently, we are conducting a prospective clinical trial as part of the In‐Vivo Monitoring project (InViMo) at the Heidelberg Ion Beam Therapy Center (HIT) in Germany. We are using an innovative, in‐house developed, non‐contact fragment tracking system with seven mini‐trackers based on the Timepix3 technology developed at CERN.This article focuses on the implementation of the mini‐tracker in Monte Carlo (MC) based on FLUKA simulations to monitor secondary charged nuclear fragments in CIRT. The main objective is to systematically evaluate the simulation accuracy for the InViMo project.The implementation involved integrating the mini‐tracker geometry and the scoring mechanism into the FLUKA MC simulation, utilizing the finely tuned HIT beam line. The systematic investigation included varying mini‐tracker angles (from 15∘$15^\circ$ to 45∘$45^\circ$ in 5∘$5^\circ$ steps) during the irradiation of a head‐sized phantom with therapeutic carbon‐ion pencil beams. To evaluate our implemented FLUKA framework, a comparison was made between the experimental data and data obtained from MC simulations. To ensure the fidelity of our comparison, experiments were performed at the HIT using the parameters and setup established in the simulations.Our research demonstrates high accuracy in reproducing characteristic behaviors and dependencies of the monitoring method in terms of fragment distributions in the mini‐tracker, track angles, emission profiles, and fragment numbers. Discrepancies in the number of detected fragments between the experimental data and the data obtained from MC simulations are less than 4% for the angles of interest in the InViMo detection system.Our study confirms the potential of our simulation framework to investigate the performance of monitoring inter‐fractional anatomical changes in patients undergoing CIRT using secondary nuclear charged fragments escaping from the irradiated patient. [ABSTRACT FROM AUTHOR]

Objective: The highly conformal carbon-ion radiotherapy is associated with an increased sensitivity of the dose distributions to internal changes in the patient during the treatment course. Hence, monitoring methodologies capable of detecting such changes are of vital importance. We established experimental setup conditions to address the sensitivity of a monitoring approach based on secondary-fragment tracking for detecting clinically motivated air cavity dimensions in a homogeneous head-size PMMA phantom in 40 mm depth., Approach: The air cavities were positioned within the entrance channel of a treatment field of 50 mm diameter at three lateral positions. The measured secondary-fragment emission profiles were compared to a reference measurement without cavities. The experiments were conducted at the Heidelberg Ion-Beam Therapy Center in Germany at typical doses and dose rates., Main Results: Significances above a detectability threshold of 2σ for the larger cavities (20 mm diameter and 4 mm thickness, and 20 mm diameter and 2 mm thickness) across the entire treatment field. The smallest cavity of 10 mm diameter and 2 mm thickness, which is on the lower limit of clinical interest, could not be detected at any position. We also demonstrated that it is feasible to reconstruct the lateral position of the cavity on average within 2.8 mm, once the cavity is detected. This is sufficient for the clinicians to estimate medical effects of such a cavity and to decide about the need for a control imaging CT., Significance: This investigation defines well-controlled reference conditions for the evaluation of the performance of any kind of treatment monitoring method and its capability to detect internal changes within head-sized objects. Air cavities with volumes from 0.31 cm3 to 1.26 cm3 were narrowed down around the detectability threshold of this secondary-fragment-based monitoring method., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective. There is an increasing interest in calculating and measuring linear energy transfer (LET) spectra in particle therapy in order to assess their impact in biological terms. As such, the accuracy of the particle fluence energy spectra becomes paramount. This study focuses on quantifying energy depositions of distinct proton, helium, carbon, and oxygen ion beams using a silicon pixel detector developed at CERN to determine LET spectra in silicon. Approach. While detection systems have been investigated in this pursuit, the scarcity of detectors capable of providing per-ion data with high spatial and temporal resolution remains an issue. This gap is where silicon pixel detector technology steps in, enabling online tracking of single-ion energy deposition. The used detector consisted of a 300 µ m thick silicon sensor operated in partial depletion. Main results. During post-processing, artifacts in the acquired signals were identified and methods for their corrections were developed. Subsequently, a correlation between measured and Monte Carlo-based simulated energy deposition distributions was performed, relying on a two-step recalibration approach based on linear and saturating exponential models. Despite the observed saturation effects, deviations were confined below 7% across the entire investigated range of track-averaged LET values in silicon from 0.77 keV µ m -1 to 93.16 keV µ m -1 . Significance. Simulated and measured mean energy depositions were found to be aligned within 7%, after applying artifact corrections. This extends the range of accessible LET spectra in silicon to clinically relevant values and validates the accuracy and reliability of the measurements. These findings pave the way towards LET-based dosimetry through an approach to translate these measurements to LET spectra in water. This will be addressed in a future study, extending functionality of treatment planning systems into clinical routine, with the potential of providing ion-beam therapy of utmost precision to cancer patients., (Creative Commons Attribution license.)

In this report, we perform structure validation of recently reported RNA phosphorothioate (PT) modifications, a new set of epitranscriptome marks found in bacteria and eukaryotes including humans. By comparing synthetic PT-containing diribonucleotides with native species in RNA hydrolysates by high-resolution mass spectrometry (MS), metabolic stable isotope labeling, and PT-specific iodine-desulfurization, we disprove the existence of PTs in RNA from E. coli, S. cerevisiae, human cell lines, and mouse brain. Furthermore, we discuss how an MS artifact led to the initial misidentification of 2'-O-methylated diribonucleotides as RNA phosphorothioates. To aid structure validation of new nucleic acid modifications, we present a detailed guideline for MS analysis of RNA hydrolysates, emphasizing how the chosen RNA hydrolysis protocol can be a decisive factor in discovering and quantifying RNA modifications in biological samples., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)