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Stepwise Topochemical Linkage of Zirconium Oxo Clusters to Yield Black Zirconia Nanocrystals
No full text二量体ジルコニウムオキソクラスターのような分子前駆体の熱変換経路を解明することは、カスタマイズされた特性を持つ機能性ジルコニアナノ材料の合理的設計に不可欠である。本研究では、ex situアニールサンプルの放射光X線二体分布関数分析を主に用い、SCXRD、TGA、FTIR、EPR分光法を補完することで、分子前駆体から最終酸化物までの詳細な段階的な構造変化を追跡した。journal articl
Performance of the LABDOS01 spectrometer in dosimetric measurements
No full textThis paper describes the performance of the LABDOS01, a silicon diode-based spectrometer suitable for dose measurements in mixed radiation fields. The instrument is currently being used in two high-altitude environmental dose monitoring projects: SAMADHA (South Atlantic Magnetic Anomaly Dosimetry at High Altitude) at Chacaltaya (Bolivia, 5240 m a.s.l.) and CORDIAL (COsmic Rays Dosimetry In Antarctic Latitudes) at the Concordia station (Antarctica, 3233 m a.s.l.). Before installing two of these devices at the measurement sites, the detectors were tested on flight routes covering a wide range of geomagnetic latitudes. The collected dosimetric data were compared with the expectations derived by the CARI-7A software, which provides the absorbed dose rate in silicon due to cosmic ray secondaries at a given position on the Earth. The measured dose rates along the flights at variable altitude and rigidity cutoff agree well with the simulated ones. By analyzing the spectrum of the energy deposited in the silicon layer, we derive an empirical method to approximately evaluate the ambient dose equivalent ∗(10), a quantity directly related to the biological damage caused by environmental radiation.journal articl
Development and demonstration of an active optical axis alignment method for divertor infrared thermography system in ITER
No full textAn active alignment method to compensate for optical axis misalignment between the in-vessel and ex-vessel optics caused by thermal expansion of the vacuum vessel during plasma operation was developed in this study. By observing the return light from an alignment pattern at the vacuum window and a calibration light source positioned at the first pupil plane inside the vacuum vessel, subsequent optical axis alignment during plasma operation can be conducted using only the return light from the alignment pattern. Testing with a prototype demonstrated that the developed alignment method can align the optical axis remotely and actively with accuracies of less than 0.03° for angular decentration, less than 1 mm for parallel decentration, and less than 5 mm for optical path length displacement.journal articl
Dose-averaged LET escalation with multi-ion therapy for head and neck cancers: A Phase I study protocol for a prospective, open-label, single-arm, single-center trial (MULTI-ION-I)
No full text頭頸部癌症例に対してマルチイオン治療を行い、生物線量分布をこれまでの炭素イオン線治療単独と同等に保ちながら正常組織の線量制約を満たすことによって安全性を維持しつつ、腫瘍標的内の線量平均LETを最適化し、目標線量平均LET中央値を70 keV/μmから段階的に増加させ、最終的には至適な線量平均LET中央値と予想される90 keV/μmを臨床的に用いる事の安全性と有効性を評価する。journal articl
Comparative Evaluation of Wavelength-Dependent Photodynamic Therapy Efficacy Using Representative Red and Near-Infrared Photosensitizers in a Single Tumor Model.
No full textIntroductionThis study aims to investigate and fairly compare the oncological therapeutic efficacy of red photodynamic therapy (Red-PDT) and near-infrared photodynamic therapy (NIR-PDT), to support the selection of suitable photosensitizers (PSs) for optimal PDT.MethodsTwo different representative PSs, trastuzumab-HiLyte Fluor™ 647 conjugate (Tra-HLF647) and trastuzumab-Indocyanine Green conjugate (Tra-ICG), activated by two laser systems at 635 nm and 808 nm, respectively, were used. To ensure a fair comparison, we used the same A4 cell line/tumor model expressing the same target, human epidermal growth factor receptor 2 (HER-2), and employed the same delivery approach. To comprehensively evaluate and compare the potential effects of Tra-HLF647-mediated Red-PDT and Tra-ICG-mediated NIR-PDT, we conducted cell viability imaging assays, intracellular reactive oxygen species (ROS) generation measurements, longitudinal monitoring of tumor volume changes, histological and immunohistochemical (IHC) analyses of tumor sections, and measurements of tumor necrotic depth.ResultsBoth PDTs exerted similar rapid cell death in cell viability imaging assays. There was no significant difference in ROS generation between cells subjected to Red-PDT and NIR-PDT. Both PDTs caused a statistically significant tumor growth delay compared to the control groups; however, no significant difference was detected between the Red-PDT and NIR-PDT groups. The H&E-stained sections of tumors that received Red-PDT and NIR-PDT showed a similar pattern of necrosis-associated features. No conspicuous tissue damage was observed in the control groups. The depth of necrosis, estimated via the coincided accumulation of a fluorescent necrosis marker (AF546-pHLIP) and utilized as an indirect index to approximate laser light penetration, was also nearly identical between tumors treated with Red-PDT and NIR-PDT.ConclusionsTarget-specific Red-PDT and NIR-PDT, using their respective PSs, demonstrated equivalent therapeutic efficacy in tumor models. These findings suggest that wavelength differences between Red-PS and NIR-PS may not critically impact treatment outcomes, offering flexibility in fluorophore selection for future PS conjugate design.journal articl
Discovery of Pyrazole-Based Positron Emission Tomography Agent that Maps Histone Deacetylase 6 (HDAC6) in the Nonhuman Primate Brain
No full textHistone deacetylase 6 (HDAC6) is a crucial target for the development of pharmaceuticals used in the treatment of neurodegenerative disorders. Here, we identified 16a as a candidate of positron emission tomography (PET) tracer for HDAC6 imaging from pyrazole derivatives, which showed strong HDAC6 affinity (Kd = 1.66 nM) and higher accumulation in the brain of wild-type mice than in HDAC6 knockout mice. Following radiolabeling with fluorine-18, PET with [18F]16a exhibited heterogeneous uptake of radioactivity, corresponding to the biological distribution of HDAC6 in the monkey brain. These radioactive distributions were homogeneously diminished by the preadministration of ACY-775, a potent inhibitor of HDAC6, suggesting that radioactive accumulation in PET images could reflect the specific binding of [18F]16a with HDAC6. Thus, [18F]16a is a promising PET tracer for HDAC6 imaging that motivates future clinical research.journal articl
Development of a CD9-Targeted Radiopharmaceutical for Imaging and Radionuclide Therapy in CD9-Positive Glioma
No full textHigh expression of CD9 (cluster of differentiation 9) is closely associated with the poor prognosis of glioma, and it is necessary to develop targeted radiopharmaceuticals for diagnosis and treatment. The therapeutic efficacy of peptide-based drugs is often limited by their rapid metabolism. This study aims to develop an integrated theranostic radiopharmaceutical capable of in vivo CD9 targeting by modifying peptides with maleimide. The CD9-binding molecule DOTA-M-P was synthesized and labeled with 68Ga and 177Lu by using an indirect labeling method. Construction of a CD9-overexpressing cell line (U87-CD9) to simulate an in vivo and in vitro model of the invasive glioma subtype before the affinity of DOTA-M-P for the CD9 protein was assessed through cellular assays. In vivo small animal PET/CT and SPECT/CT imaging and biodistribution studies were conducted to verify pharmacokinetics and tumor-targeting retention capabilities. DNA damage assays and Western blot analyses were employed to explore the therapeutic mechanisms. Radioligand therapy studies were performed to evaluate the therapeutic efficacy. Then OLINDA/EXM was employed to estimate the effective dose to human organs from 177Lu-DOTA-M-P for assessing its dose safety. In vitro cellular assays demonstrated that DOTA-M-P exhibits a moderate affinity for CD9. In vivo imaging studies demonstrated the modest targeting and retention capabilities of DOTA-M-P. Biodistribution experiments indicated that DOTA-M-P is primarily metabolized via the kidneys. Mechanistic studies suggested that 177Lu-DOTA-M-P induces DNA damage, thereby activating the mitochondrial apoptotic pathway. Targeted radioligand therapy results revealed that a single dose of 18.5 MBq of 177Lu-DOTA-M-P significantly inhibited U87-CD9 tumor growth. The effective doses for all human organs were estimated to be below the single-dose limit (21 CFR 361.1) established by U.S. regulatory standards, demonstrating a favorable safety profile for clinical translation. We developed a CD9-targeted peptide precursor, DOTA-M-P, enabling dual-functional radionuclide imaging and therapy for glioma, with human dose estimates supporting personalized regimens and theranostic applications.journal articl
Spectroscopic analysis and internal dose assessment in lung counting for reactor-grade Pu compounds
No full textInternal contamination with plutonium (Pu) isotopes represents one critical exposure scenario in nuclear fuel cycle facilities. Lungcounting is commonly employed as the initial individual monitoring method following inhalation of Pu. Due to the low detection sensitivity for characteristic X-rays emitted by Pu isotopes, the γ-ray emitted by coexisting 241Am is typically used as a surrogate for measurement. However, it is essential to establish clear procedures applicable in cases of severe internal exposure. In this study, key challenges associated with lung counting and dose assessment were examined, focusing on an inhalation event of reactor-grade Pu compounds containing 238Pu to 242Pu. These challenges included: complex spectral peak analysis; increased minimum detectable activity for Pu isotopes due to interference from 241Am; and evaluation of the minimum assessable dose considering Pu isotopic composition. Based on these considerations, procedures from lung counting to internal dose assessment were refined to support emergency response.journal articl
Recent trends in cosmic radiation exposure onboard aircraft: effects of the COVID-19 pandemic on Japanese in-flight doses
No full textBackground: Galactic cosmic radiation (GCR) is a naturally occurring environmental radiation that originates from outer space. GCR is modulated by solar activity, and its intensity increases with increasing geomagnetic latitude and altitude, reaching a peak of up to approximately 20 km in the atmosphere. Therefore, commercial flight passengers (flyers) are exposed to elevated levels of cosmic radiation while flying onboard commercial aircraft. Although the recent COVID-19 pandemic, which began in early 2020, is believed to have significantly affected public exposure to cosmic radiation, this impact is yet to be quantified.Methods: Based on the official records of Japanese flyers, their annual percapita doses (APCDs) of cosmic radiation exposure on international and domestic flights were calculated using the established code JISCARD EX over a 7-year period from 2014 to 2020 (including the first year of the pandemic). For estimating the APCDs on international flights, the world was divided into eight regions. The aviation route dose to a representative city in each region was determined at three cruising altitudes: 34,000 ft. (10.4 km), 37,000 ft. (11.3 km), and 40,000 ft. (12.2 km).Results: At a typical cruising altitude of 37,000 ft., the flyer-average APCD from international flights was estimated to be approximately 60 μSv y−1, while the APCD from domestic flights was approximately 2 μSv y−1 over the target period, including the pandemic year (2020). These results indicate that the distribution of Japanese travel destinations did not change significantly during the pandemic period. In contrast, the population-average APCD significantly decreased from approximately 10 μSv y−1 in the pre-pandemic period (2014–2019) to 2 μSv y−1 in 2020, representing a reduction of more than 80%, which corresponds to a decline in the number of travelers.Conclusion: The results of this study indicate that the population-average APCD of Japanese flyers decreased significantly during the COVID-19 pandemic, while the flyer-average APCD remained largely unchanged. Further studies will be performed to determine APCDs for the subsequent period and to assess the overall effect of the pandemic on public health.journal articl
Range verification of a 10C ion beam: Feasibility of Compton imaging of 718 keV gamma rays
No full textRadioactive ion beams can be considered for range verification in carbon therapy as an ideal method using in-beam positron emission tomography (PET) imaging since ion beam ranges can be directly visualized. In particular, a PET image with acceptable quality can be obtained for a10C ion beam even for an in-beam PET scan time of approximately 1 min, owing to the short half-life (19.3 s) of 10C. In addition, a 718 keV photon is emitted almost simultaneously with the positron decay, and the feasibility of its direct localization based on triple gamma imaging (i.e., the β+-gamma coincidence) has been shown by whole gamma imaging (WGI). The WGI system is realized as a dual-detector ring geometry, which can work in three modes: PET, Compton imaging and triple gamma imaging. However, the range verification performance for all three modes has not yet been assessed. In particular, the potential of Compton imaging, which is not influenced by the relatively long positron range of 10C, has not been shown. In this work, we focused on comparing the performance of Compton imaging with that of PET for a10C ion beam using WGI. First, we irradiated a polymethyl methacrylate (PMMA) phantom with a10C beam under in-beam WGI measurement in the carbon therapy facility of the heavy ion medical accelerator in Chiba (HIMAC) and compared the measured images with the depth dose. We then modelled our WGI system by Geant4 to evaluate the influence of the scatterer energy resolution on the imaging performance of the WGI for a10C point source and on the accuracy of range verification for a10C pencil beam. Energy resolutions of 17 % (current WGI) and 1 % (advanced WGI) at 511 keV photons were considered for the scatterer detectors. The measurements revealed small shifts between the Bragg peak position and the positions of the peaks for PET, Compton and triple gamma imaging. The worst shift of 3.1 ± 0.3 mm was observed at 80 % of the peaks for Compton imaging, which may be explained by the undesirable poor energy resolution of the scatterer detectors. In the simulation, spatial resolutions of 5.6 mm and 2.4 mm were obtained for the Compton mode of the current and advanced WGIs, respectively, for the simulated 10C point source at the Center of the field of view (FOV). The shifts in the Bragg peak position and the position of the Compton peak at the 80 % level considerably improved for the advanced WGI for the simulated PMMA phantom irradiated with a10C pencil beam. The shifts at the 80 % peak level were 0.1 mm for the PET and Compton modes of the advanced WGI. The positron range-free did not compensate for the limited energy resolution in Compton imaging, and the accuracy of the Compton image was comparable to that of the PET image when the energy resolution of the scatterer detector was improved. Sensitivity enhancement by combining PET with Compton imaging and simultaneous tumor damage assessment with range verification are expected to be possible applications of WGI in 10C beam irradiation.journal articl