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Japanese Journal of Clinical Oncology Jun 2024Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison...
BACKGROUND
Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison with traditional proton beam therapy, scanning proton beam therapy is effective in delivering proton beams to irregularly shaped tumors, reducing excessive radiation exposure to the alimentary tract during the treatment of liver cancer.
METHODS
In this study, we utilized positron emission tomography/computed tomography (PET/CT) imaging to assess the total amount of radiation to the alimentary tract during liver cancer treatment with proton beam therapy, involving the administration of complex irradiation in 13 patients.
RESULTS
This approach resulted in the prevention of excess radiation. The planned radiation restraint doses for the colon exhibited a significant correlation with the PET values of the colon (correlation coefficient 0.8384, P = .0003). Likewise, the scheduled radiation restraint doses for the gastroduodenum were correlated with the PET values of the gastroduodenum (correlation coefficient 0.5397, P = .0569).
CONCLUSIONS
PET/CT conducted after proton beam therapy is useful for evaluating excess radiation in the alimentary tract. Proton beam therapy in liver cancer, assessed via PET/CT, effectively reduced alimentary tract radiation, which is vital for optimizing treatments and preventing excess exposure.
PubMed: 38943456
DOI: 10.1093/jjco/hyae085 -
Cell Research Jun 2024
PubMed: 38942816
DOI: 10.1038/s41422-024-00993-6 -
Nature Communications Jun 2024Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for the preparation of chiral α-substituted propionic acids. However, research...
Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for the preparation of chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, is still insufficient in both academic and industrial contexts. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of α-substituted acrylic acids affording the corresponding chiral α-substituted propionic acids with up to 99.4% ee (enantiomeric excess) and 10,000 S/C (substrate/catalyst). In particular, this method can be used to obtain (R)-dihydroartemisinic acid with 99.8:0.2 dr (diastereomeric ratio) and 5000 S/C, which is an essential intermediate for the preparation of the antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments and DFT (Density Functional Theory) calculations, which indicate that the protonolysis of the C-Ni bond of the key intermediate via an intramolecular proton transfer from the carboxylic acid group of the substrate, is the rate-determining step.
PubMed: 38942809
DOI: 10.1038/s41467-024-49801-0 -
Methods in Enzymology 2024Magnesium ions (Mg) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without...
Magnesium ions (Mg) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without cleaving the diphosphate group, instead initiating the reaction through protonation. In our recent research, we discovered a novel class II sesquiterpene cyclase in Streptomyces showdoensis. Notably, we determined its crystal structure and identified Mg within its active site. This finding has shed light on the previously elusive question of Mg binding in class II terpene cyclases. In this chapter, we outline our methods for discovering this novel enzyme, including steps for its purification, crystallization, and kinetic analysis.
Topics: Magnesium; Sesquiterpenes; Streptomyces; Binding Sites; Kinetics; Bacterial Proteins; Catalytic Domain; Crystallography, X-Ray; Structure-Activity Relationship; Crystallization; Carbon-Carbon Lyases
PubMed: 38942506
DOI: 10.1016/bs.mie.2024.02.018 -
Radiotherapy and Oncology : Journal of... Jun 2024To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor...
PURPOSE
To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber.
METHODS AND MATERIALS
227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector.
RESULTS
Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ± 3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ± 0.8 Gy/s and mean local average dose rate of 160.6 ± 3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose.
CONCLUSION
In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.
PubMed: 38942121
DOI: 10.1016/j.radonc.2024.110404 -
Radiotherapy and Oncology : Journal of... Jun 2024As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques...
BACKGROUND AND PURPOSE
As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing.
MATERIALS AND METHODS
A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared.
RESULTS
Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2).
CONCLUSION
This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.
PubMed: 38942120
DOI: 10.1016/j.radonc.2024.110414 -
Physics in Medicine and Biology Jun 2024Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are...
Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. CPPT treatments must balance two competing goals: 1) deliver a larger dose in the proton fractions to reduce integral dose, and 2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing IMPT and IMRT plans based on their cumulative biologically effective dose (BED). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BEDby 29% and the mean liver BEDby 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BEDand mean liver BEDare reduced by 28% and 58%, respectively, compared to IMRT-only plans. CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources. .
PubMed: 38942008
DOI: 10.1088/1361-6560/ad5d48 -
Physics in Medicine and Biology Jun 2024Particle therapy treatments are currently limited by uncertainties of the delivered dose. Verification techniques like Prompt-Gamma-Timing-based Stopping Power...
Particle therapy treatments are currently limited by uncertainties of the delivered dose. Verification techniques like Prompt-Gamma-Timing-based Stopping Power Estimation (PGT-SPE) may allow for reduction of safety margins in treatment planning. Approach: From Prompt-Gamma-Timing measurements, we reconstruct the spatiotemporal distribution of prompt gamma emissions, which is linked to the average motion of the primary particles. The stopping power is determined by fitting a model of the average particle motion. Here, we compare a previously published implementation of the particle motion model with an alternative formulation and present two formulations to automatically select the hyperparameters of our procedure. The performance was assessed using Monte-Carlo simulations of proton beams (60 MeV to 219 MeV) impinging on a homogeneous PMMA phantom. Main results: The range was successfully determined within a standard deviation of 3 mm for proton beam energies from 70 MeV to 219 MeV. Stopping power estimates showed errors below 5 % for beam energies above 160 MeV. At lower energies, the estimation performance degraded to unsatisfactory levels due to the short range of the protons. The new motion model improved the estimation performance by up to 5 % for beam energies from 100 MeV to 150 MeV with mean errors ranging from 6 % to 18 %. The automated hyperparameter optimization matched the average error of previously reported manual selections, while significantly reducing the outliers. Significance: The data-driven hyperparameter optimization allowed for a reproducible and fast evaluation of our method. The updated motion model and evaluation at new beam energies bring us closer to applying PGT-SPE in more complex scenarios. Direct comparison of stopping power estimates between treatment planning and measurements during irradiation would offer a more direct verification than other secondary-particle-based techniques.
PubMed: 38941994
DOI: 10.1088/1361-6560/ad5d4b -
Journal of Colloid and Interface Science Jun 2024Electrochemical nitrate reduction reaction (NORR) offers a cost-effective and environmentally friendly method to simultaneously yield valuable NHand alleviate...
Electrochemical nitrate reduction reaction (NORR) offers a cost-effective and environmentally friendly method to simultaneously yield valuable NHand alleviate NOpollution under mild operating conditions.However, this complicated eight-electron reaction suffers from low selectivity and Faradaic efficiency, which highlight the importance of developing efficient catalysts, but still a critical challenge. Here, a theoretical screening is performed on transition metal-tetragonal carbon nitride (TM@T-CN) as active and selective electrocatalysts for NORR, where detailed reaction mechanisms and activity origins are explored. In addition, five-step screening criteria and volcano plots enable fast prescreening among numerous candidates.We identify that V@T-CN and Cr@T-CN are promising candidates with low overpotentials and high selectivity and stability. In particular, a significant negative correlation between the adsorption strength ofnitrate and the Gibbs free energy for the last proton-electron coupling step (*NH→*NH) was existed, which is considerably advantaged to track the activity trend and reveal the origin of activity. This work provides theoretical insights into the rational design of TM-N/C catalysts for NORR andpaves a valuable electrochemical screening framework for other multi-step reactions.
PubMed: 38941929
DOI: 10.1016/j.jcis.2024.06.178 -
Oral Oncology Jun 2024
PubMed: 38941874
DOI: 10.1016/j.oraloncology.2024.106912