National Institutes for Quantum and Radiological Science and Technology
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Low-background Alpha Imaging System Using a CMOS Camera with Suppressed Dark Current
No full textTargeted alpha therapy (TAT) using short-lived radionuclides like ²¹¹At demands rapid and quantitative analysis of both activity and chemical forms across a wide dynamic range. However, existing imaging systems such as imaging plates (IPs) or standard CMOS-based setups suffer from significant noise accumulation and demand long measurement times, particularly under low-activity conditions. We report on the development of NuS-AGS, a low-background alpha imaging system using a CMOS sensor with hardware-level dark current suppression. Compared to a conventional CMOS camera, NuS-AGS exhibited ~97% suppression of dark signal accumulation up to 200 seconds without the need for post-processing subtraction. The system achieved 148 μm spatial resolution, excellent linearity (R² = 0.996) for 1.10–6.60 kBq of 211At, and stable half-life measurements consistent with ²¹¹At. Moreover, it resolved three chemical species of ²¹¹At using thin-layer chromatography within 10 minutes, significantly outperforming IPs (2.8% of measurement time). These results demonstrate that NuS-AGS enables high-sensitivity, low-background alpha imaging suitable for both radiochemical research and clinical quality control workflows.journal articl
Longitudinal assessment of DREADD expression and efficacy in the monkey brain.
No full textDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) offer a powerful means for reversible control of neuronal activity through systemic administration of inert actuators. Because chemogenetic control relies on DREADD expression levels, understanding and quantifying the temporal dynamics of their expression is crucial for planning long-term experiments in monkeys. In this study, we longitudinally quantified in vivo DREADD expression in macaque monkeys using positron emission tomography with the DREADD-selective tracer [C]deschloroclozapine (DCZ), complemented by functional studies. Twenty macaque monkeys were evaluated after being injected with adeno-associated virus vectors expressing the DREADDs hM4Di or hM3Dq, whose expression was quantified as changes in [C]DCZ binding potential from baseline levels. Expression levels of both hM4Di and hM3Dq peaked around 60 days post-injection, remained stable for about 1.5 years, and declined gradually after 2 years. Significant chemogenetic control of neural activity and behavior persisted for about 2 years. The presence of protein tags significantly influenced expression levels, with co-expressed protein tags reducing overall expression levels. These findings provide valuable insights and guidelines for optimizing the use of DREADDs in long-term primate studies and potential therapeutic applications.journal articl
Effects of reflectors on the imaging performance of a mouse brain PET scanner with staggered 3-layer DOI detectors
No full textBackground: For mouse brain positron emission tomography (PET), good spatial resolution and depth-of-interaction (DOI) information are necessary. Spatial and DOI resolutions of PET systems are highly affected by reflector materials. Nevertheless, the effects of reflector materials on the imaging performance have not been investigated in PET system levels.Purpose: Here, we systematically investigate the effects of reflector materials on the imaging performance of a mouse brain PET scanner using staggered 3-layer DOI detectors. Methods: We separately constructed mouse brain PET scanners with two reflector materials of barium sulfate (BaSO4) powder and enhanced specular reflector (ESR) film. The PET inner diameter (53 mm), crystal pitch (1 mm) and crystal layer thickness (4/4/7 mm) were the same for BaSO4 and ESR. Physical and imaging performance of the PET scanners were evaluated with the same silicon photomultipliers, and front-end electronics.4.Results: The system coincidence timing resolution with ESR (3.6 ns) was twice as good as that with BaSO4. (7.0 ns). However, the average radial resolution with BaSO4 (0.96 mm) was 0.2 mm better than that with ESR (1.16 mm) because of the reduced crystal decoding error. A narrow energy window (440-560 keV) effectively improved the valley-to-peak ratio of submillimeter rod structures especially for BaSO4 due to the reduced inter crystal scattering events, although at the expense of sensitivity. Conclusions: We found BaSO4 provided better spatial resolution and imaging performance over ESR for the mouse brain PET scanner with staggered 3-layer DOI detectors.journal articl
64Cu-Labeled Stapled Peptide-Based Radiopharmaceuticals Targeting MDM2/MDMX for Pan-p53 Tumors
No full textThe development of ideal peptide-based radiopharmaceuticals faces critical bottlenecks, primarily due to limited cellular internalization and insufficient deep tissue penetration of peptide carriers. To address this, we developed an intracellular targeting and DNA-adjacent radiotherapeutic strategy using stapled peptides. The MDM2/MDMX-targeting stapled peptide-based radiopharmaceuticals, denoted as [64Cu]Cu-DOTA-STP, exhibited prolonged circulation in the bloodstream and slow systemic clearance. Furthermore, in vitro studies demonstrated that nearly 50% of administered [64Cu]Cu-DOTA-STP was internalized, achieving efficient intracellular accumulation. In addition, [64Cu]Cu-DOTA-STP demonstrated high tumor accumulation, with a standard uptake value of up to 9.39 ± 1.52%ID/g. Finally, targeted radionuclide therapy confirmed that [64Cu]Cu-DOTA-STP effectively inhibited tumor growth, irrespective of p53 phenotypes. Taken together, this study leveraged PET imaging as a noninvasive and longitudinal tool to elucidate the in vivo fate of stapled peptides and demonstrated that stapled peptides can serve as ideal vehicles for developing intracellular protein-targeting radiopharmaceuticals, achieving efficient 64Cu-based targeted radionuclide therapy.journal articl
A GPU‐based Monte Carlo model for water radiolysis under ultra‐high dose rate irradiation: Development and validation with MPEXS2.1‐DNA
No full textBackgroundFLASH radiotherapy using ultra‐high dose rates (UHDR, > 40 Gy/s) demonstrates significant healthy‐tissue sparing while maintaining tumor‐control effectiveness. However, the underlying mechanisms remain unclear, with hypotheses suggesting that reductions in reactive oxygen species (ROS) yields could contribute to the FLASH effect. Direct experimental measurements of ROS dynamics under UHDR conditions are challenging, making Monte Carlo simulations valuable complementary tools for tracking individual water radiolysis species over time.PurposeTo enable a mechanistic investigation of ROS yield reductions under UHDR conditions, we developed a GPU‐based water radiolysis simulation platform capable of modeling key radiation chemistry processes.MethodsUsing our MPEXS2.1‐DNA framework with step‐by‐step molecular tracking, we simulated sequential 55 MeV proton irradiation in a 1 × 1 × 1 µm3 target volume within a 2 × 2 × 2 µm3 water phantom filled with neutral pH water at dose rates ranging from 0.02 Gy/s to 500 Gy/s, with a total absorbed dose of 10 Gy. Simulations were performed under oxygenated (pO2 = 25%, 239.4 µM) and deoxygenated (pO2 = 0%) conditions without additional scavengers. Radiation chemical yields (G values, species/100 eV) of hydroxyl radicals, hydrated electrons, and hydrogen peroxide were calculated at time points from 1 ms to 1000 s post‐irradiation. Statistical analysis was performed using 1000 independent sequential proton irradiation scenarios per dose rate condition, processed in parallel on a single GPU. Results were compared with published experimental data.ResultsThe calculated dose rate dependence of the G values of hydroxyl radicals showed agreement with experimental data, with relative G values decreasing monotonically from 1.0 at 0.02 Gy/s to approximately 0.12 at 500 Gy/s at 10 ms post‐irradiation. Our simulations revealed that intertrack chemical reactions between neighboring proton tracks occurred, leading to decreases in the G values of hydroxyl radicals through enhanced radical‐radical interactions. The G values of hydrated electrons remained constant (G ≈ 2.5 species/100 eV) across all dose rates under deoxygenated conditions, consistent with experimental observations. Oxygen consumption followed a depletion rate of 0.028%/Gy (0.27 µM/Gy), in agreement with experimental measurements, but was insufficient to cause significant depletion at typical UHDR doses (10–40 Gy). Additionally, the calculated G values of hydrogen peroxide increased by 20% with dose rate (contrary to measured decreases of 20%–40%), suggesting the presence of competitive reaction pathways not included in current models.ConclusionsWe developed a GPU‐based computational framework for water radiolysis simulations under UHDR conditions using MPEXS2.1‐DNA. Our step‐by‐step approach enabled spatially precise tracking of intertrack reactions among radiolysis species originating from different proton tracks, a capability not achievable with conventional simplified methods. Additionally, we demonstrated that large‐scale statistical analysis is computationally feasible under UHDR conditions through GPU acceleration. Our results successfully reproduced the experimental trends for the G values of hydroxyl radicals and hydrated electrons. Oxygen depletion rates also showed good agreement with experimental measurements. However, the discrepancy between simulated and measured G values of hydrogen peroxide indicates the need to incorporate additional competitive reactions, potentially including third‐order mechanisms, for future UHDR modeling studies.journal articl
Stereoisomerism-controlled Packing in Ladder-type Indacenodithieno[3,2-b]thiophene Crystals
No full textStereochemistry is a potent way to direct the molecular packing in condensed phases. Here, we synthesized the enantiopure, racemic and achiral isomers of p-type small molecule i.e. indacenodithieno[3,2-b]thiophene (IT) to understand the impact of stereochemistry on molecular packing and solid state properties. In the solution state, the optical properties remain nearly identical among the isomers, however significant difference was observed in the condensed phase. X-ray diffraction pattern revealed enantiopure isomers were more tightly packed and exhibited strong π-stacking relative to their racemic and achiral counterparts. Two dimensional arrangement of the stacked enantiopure isomers gives more dense-packed crystalline phases than an achiral analog, which is unusual anti-Wallach type condensed phases. The enantiopure one exhibited two times higher photoconductivity than its achiral or racemic analogues, as well as showing high electron spin polarizability (~ 75%) with electrical current throughput (100 nA). The result highlights the role of stereochemistry as a key strategy to direct the condensed phase packing and properties in conjugated crystals.journal articl
ICRU Report 100, Radiation Protection Dosimetry for External Sources of Ionizing Radiation
No full textOver the past 100 years, the International Commission on Radiation Units and Measurements (ICRU) has provided scientific insight and guidance to the radiation protection community. As with any scientific endeavor, the development, enhancement, recommendations, and guidance evolve as the understanding of the underlying principles and physics improves. Throughout this evolution, the ICRU has consistently updated its recommendations to the radiation protection community through various reports. Central to radiation protection is the measurement, with instruments and personal dosimeters, of radiation fields. These measurements may be of fundamental physical quantities such as the number and energy of radiation particles that traverse a region or of subsequent effects of this radiation field such as ionization produced in air or absorbed dose delivered to a specific region. The recommendations of the ICRU have evolved and adapted in accordance with the increased understanding of fundamental physical processes and the effects of exposure to radiation to meet the challenges faced by radiation protection professionals. Practical radiation protection relies on the measurement of operational quantities to guide the process of optimization of exposure and to demonstrate that dose limits and constraints have been respected. This is the field of radiation protection dosimetry, and the measuring instruments are dosimeters and monitors, the latter used for the measurement of dose rates.The present report aims to provide an overview of the currently available techniques for radiation protection dosimetry of external exposure. It bridges the gap between textbooks of radiation protection or detector technologies and the current state of the science as reported in reviewed publications and technical manuals of manufacturers. It may also serve as an introduction to newcomers in radiation protection, giving them an overview of the wide spectrum of applications, techniques, and instruments in external radiation protection.After an introduction to protection and operational quantities in radiation protection, notably personal and ambient dose equivalent as defined in ICRU Report 51 (Allisy et al., 1993) and personal and ambient dose defined in ICRU Report 95 (Bartlett et al., 2020), two sections focus on external dosimetry of photons, electrons and neutrons. In these sections, the impact of the operational quantities introduced in ICRU Report 95 on dosimeters and instruments are shown and discussed. These are followed by a section on dosimetry techniques for specific situations which are outside the normal operating range of the dosimeters described in the previous sections. This encompasses situations where no single radiation type dominates the overall exposure, where the energy of radiation is very high, or where the time structure of the radiation is pulsed. The section on accident dosimetry covers very high doses and dose rates. Today, computer simulation plays a cardinal role in radiation protection dosimetry: conversion coefficients of the operational quantities for the calibration of dosimeters are calculated by Monte Carlo simulation and new dosimeter types are designed virtually on the computer before the construction of prototypes. A full section is dedicated to this development. Finally, type testing and calibration of dosimeters and monitors are described in detail. Two appendices describe evaluation algorithms for dosimeters and reporting and recordkeeping of the results of dosimetry.journal articl
Evaluation of Physiological Characteristics of in vivo AGN Probe Using Multimodal Imaging
No full textMotivation: Monitoring the enzymatic activity of APN in tumors non-invasively can improve cancer diagnostics and therapy. A hyperpolarized AGN probe is a key biomarker for APNGoal(s): This study aimed to validate the physiological characteristics of AGN probes in vivoApproach: We used hyperpolarized C MRS and EPSI to measure APN activity in tumors with varying APN expression. DCE-MRI, DWI, and EPRimaging to evaluate several tumor physiological parametersResults: The AGN probe distinguished high and low APN-expressing tumors, even in low permeability and hypoxic regions, showing promise forpersonalized cancer treatmentImpact: The hyperpolarized AGN probe provides a novel, non-invasive method for real-time monitoring of APN activity in tumors, even in hypoxic and low-perfusion regions, thus providing therapeutic strategies and personalized cancer treatmentconference pape
CHARACTERIZATION OF BEAM OPTICS CONSIDERING FRINGE FIELDS OF QUADRUPOLE MAGNETS IN A LIPAC 5 MEV BEAMLINE
No full textThis paper investigates the effect of the fringe fields of quadrupole magnets (quads) on the beam optics of a 5 MeV beamline in the Linear IFMIF Prototype Accelerator (LIPAc). During the early stages of the beam commissioning, we observed particle losses and differences in the rms beam size between measurements and simulations, despite optimizing the beam optics using the hard-edge model for all quads. To address these issues, we incorporate quad field maps in the beam optics. We also calibrate each quad conversion coefficient from magnetic gradients g to excitation currents I (GtoI) with a 5 MeV deuteron beam. This approach allows us to achieve a matched beam and reduce particle losses. We present the difference in the transfer matrices between the hard-edge models and the field maps, along with the calibration method of each GtoI of the quads with the deuteron beam. We also compare the simulated and measured beam sizes.conference pape
高度化されたタンパク質単結晶用中性子回折装置BIX-3,4の現状
No full text量子科学技術研究開発機構（QST）は、タンパク質などの生体高分子を測定対象とするBIX-3, BIX-4（日本原子力研究開発機構・研究用原子炉JRR-3に設置）を運用している。両装置では直接観察された水素原子や水和水の構造情報から、タンパク質の機能発現に必須なプロトン化状態の決定や低障壁水素結合の生体高分子における初めての観察などの成果を上げてきた。さらに近年、試料対象や回折データ測定可能領域を広げるための以下のような高度化を実施した。BIX-3では、二段式弾性湾曲Si完全結晶モノクロメータを導入することで装置測定分解能をサブÅまで随時拡大可能とした。通常測定モード（d-min=1.5Å）ではSi(111)結晶、高分解能測定モード（d-min=0.81Å）ではSi(311)結晶を随時切替える機構となっている。実際に、タンパク質結晶から世界最高分解能（0.9Å）の中性子回折データセット取得に成功した。一方BIX-4では、冷中性子を用いることで測定可能となる試料結晶の格子長を最大160Åに拡張させた。回折装置本体は従来設置のJRR-3炉室から同ビームホール・冷中性子ビームライン（C1-3ビームポート）へ移設され、利用2θ-Mを可変とする機構が導入された。本発表では、中性子回折データ取得状況及び両装置整備の現状の詳細を報告する。日本蛋白質科学会第25回年会conference poste