Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “RADIOTHERAPY”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3

Results of a Geant4 benchmarking study for bio‐medical applications, performed with the G4‐Med system

Geant4, a Monte Carlo Simulation Toolkit extensively used in bio-medical physics, is in continuous evolution to include newest research findings to improve its accuracy and to respond to the evolving needs of a very diverse user community. In 2014, the G4-Med benchmarking system was born from the effort of the Geant4 Medical Simulation Benchmarking Group, to benchmark and monitor the evolution of Geant4 for medical physics applications. The G4-Med system was first described in our Medical Physics Special Report published in 2021. Results of the tests were reported for Geant4 10.5. Purpose In this work, we describe the evolution of the G4-Med benchmarking system. Methods The G4-Med benchmarking suite currently includes 23 tests, which benchmark Geant4 from the calculation of basic physical quantities to the simulation of more clinically relevant set-ups. New tests concern the benchmarking of Geant4-DNA physics and chemistry components for regression testing purposes, dosimetry for brachytherapy with a 125 I source, dosimetry for external x-ray and electron FLASH radiotherapy, experimental microdosimetry for proton therapy, and in vivo PET for carbon and oxygen beams. Regression testing has been performed between Geant4 10.5 and 11.1. Finally, a simple Geant4 simulation has been developed and used to compare Geant4 EM physics constructors and physics lists in terms of execution times. Results In summary, our EM tests show that the parameters of the multiple scattering in the Geant4 EM constructor G4EmStandardPhysics_option3 in Geant4 11.1, while improving the modeling of the electron backscattering in high atomic number targets, are not adequate for dosimetry for clinical x-ray and electron beams. Therefore, these parameters have been reverted back to those of Geant4 10.5 in Geant4 11.2.1. The x-ray radiotherapy test shows significant differences in the modeling of the bremsstrahlung process, especially between G4EmPenelopePhysics and the other constructors under study (G4EmLivermorePhysics, G4EmStandardPhysics_option3, and G4EmStandardPhysics_option4). These differences will be studied in an in-depth investigation within our Group. Improvement in Geant4 11.1 has been observed for the modeling of the proton and carbon ion Bragg peak with energies of clinical interest, thanks to the adoption of ICRU90 to calculate the low energy proton stopping powers in water and of the Linhard–Sorensen ion model, available in Geant4 since version 11.0. Nuclear fragmentation tests of interest for carbon ion therapy show differences between Geant4 10.5 and 11.1 in terms of fragment yields. In particular, a higher production of boron fragments is observed with Geant4 11.1, leading to a better agreement with reference data for this fragment. Conclusions Based on the overall results of our tests, we recommend to use G4EmStandardPhysics_option4 as EM constructor and QGSP_BIC_HP with G4EmStandardPhysics_option4, for hadrontherapy applications. The Geant4-DNA physics lists report differences in modeling electron interactions in water, however, the tests have a pure regression testing purpose so no recommendation can be formulated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Synthesis and Characterization of Radio-Halogenated Talazoparib Analogues for Imaging and Radioligand Therapy

Abstract Talazoparib (TZ) is a potent poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that uniquely traps PARP complexes at sites of single-strand DNA damage thereby offering opportunities for targeted radioligand therapy. Radiolabeled halogenated TZ derivatives were synthesized using boronic ester precursors to enable incorporation of diagnostic and therapeutic radionuclides: 18F for PET imaging, 77Br for Auger electron radiotherapy, and 211At for targeted alpha radiotherapy. Copper-mediated radio-halogenation afforded racemic 18F-TZ, 77Br-TZ, and 211At-TZ in sufficient radiochemical yields (4.3 ± 2.6%, n = 33; 29.0 ± 12.0%, n = 4; 3.6 ± 3.8%, n = 9, respectively), ∼99% radiochemical purity and proven stability under formulation conditions. Molecular dynamics simulations of halo-TZ derivatives predicted an inverse relationship between halogen size and PARP1 binding affinity. Indeed, cell uptake of radio-halogenated TZ analogues indicated selective uptake in a panel of cell types that correlated with PARP1 levels but was inversely related to the atomic radii of the halogen series. Despite modest specific activity and specific uptake, 77Br-TZ showed significant cytotoxicity. Further investigation of 18F-TZ with 77Br-TZ as a radiotheranostic pair will be facilitated by the synthetic schemes herein.

Muzzioli, Riccardo [The University of Texas MD And↗

A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline

Abstract Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 10 7 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Feasibility of a multigroup Boltzmann–Fokker–Planck solution for electron beam dose calculations

Legacy nuclear-reactor Boltzmann solvers start clinical deployment as an alternative to Monte Carlo (MC) codes and Fermi–Eyges semiemprical models in radiation oncology treatment planning. Today’s certified clinical solvers are limited to photon beams. In this paper, ELECTR, a state-of-the-art multigroup electron cross sections generation module in NJOY is presented and validated against Lockwood’s calorimetric measurements, EGS-nrc and GEANT-4 for 1–20 MeV unidirectional electron beams. The nuclear-reactor DRAGON-5 solver is upgraded to access the library and solve the Boltzmann–Fokker–Planck (BFP) equation. A variety of heterogeneous radiotherapy and radiosurgery phantom configurations were used for validation purpose. Case studies include a thorax benchmark, that of a typical breast Intra-Operative Radiotherapy and a high-heterogeneity patient-like benchmark. For all beams, 100% of the water voxels satisfied the American Association of Physicists in Medicine accuracy criterion for a BFP-MC dose error below 2%. At least, 97.0% of adipose, muscle, bone, lung, tumor and breast voxels satisfied the 2% criterion. The average BFP-MC relative error was about 0.56% for all voxels, beams and materials combined. By irradiating homogeneous slabs from Z = 1 (hydrogen) to Z = 99 (einsteinium), we reported performance and defects of the CEPXS mode [US. Sandia National Lab., SAND-89-1685] in ELECTR for the entire periodic table. For all Lockwood’s benchmarks, NJOY-DRAGON dose predictions are within the experimental data precision for 98% of voxels.

42 ENGINEERING↗

Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

Some immune response are effected through immunoglobulins (Ig), of which five classes have been recognized, namely, IgA, IgD, IgE, IgG, and IgM. Auto-antibodies associated with rheumatoid arthritis, termed rheumatoid factors (RF) react with antigenic determinants on IgG heavy chains. RF has predominant but not complete IgM specificity. This auto-antibody response was not detected in treated patients with primary brain tumors (where tissue is sequestered from the immune system by an intact bloodbrain barrier) or with multiple myeloma where humoral immunity is usually impaired. In addition, the prevalence of RF is not increased with solid tumors prior to initiation of chemotherapy or radiotherapy. It is proposed that RF is related to prior chemotherapy or radiotherapy of tumors anatomically accessible to immunologic tissues capable of antibody responses. A primary IgG response occurs, antigen-antibody complexes form, complexed IgG becomes immunologic, and an RF response results.

Towmey, J. J.↗

Depth-dose relations for heavy ion beams

Radiation transport of heavy ions in matter is of interest to radiological protection in space and high-altitude aircraft. In addition, heavy ion beams are expected to be of advantage in radiotherapy since their characteristic Bragg curve allows a relative reduction of the dose in reaching a tumor site and the near elimination of exposure beyond the tumor region as the beam exits the body. Furthermore, the radioresistance of tumorous cells due to their hypoxic state may be reduced or eliminated by the high specific ionization of heavy ion beams. The depth-dose distribution of heavy ion beams consists of energy deposited by the attenuated primary beam with its characteristic Bragg curve and a relatively unstructured background due to secondary radiations produced in nuclear reactions. As the ion mass increases, the secondary contribution becomes more structured and may add significantly to the Bragg peak of the primary ions. The result for heavy ions (z greater than 20) is a greatly broadened Bragg peak region, especially in comparison to straggling effects, which may prove to be of importance in radiotherapy and biomedical research.

Wilson, J. W.↗

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Non-NASA Center↗

Ionizing Radiation from Ex Vivo Sterilization Diminishes Collagen Integrity and Vertebral Body Mechanics

Clinical exposure to ionizing radiation could put cancer radiotherapy or bone allograft patients at an increased risk of fracture. In these applications, ionizing radiation levels can range from accumulative 50 Gy for radiotherapy cancer treatment, to acute 35,000 Gy for allograft sterilization. Ionizing radiation has been shown to decrease bon equality through reduced strength and post-yield properties and degrade collagen integrity through either increased crosslinks (advanced glycation end products, AGEs)or fragmentation. It is unclear which collagen structural change accounts for reduced strength. The dose-dependent effect of ionizing radiation on mechanical and biochemical properties of whole bones are not well understood, particularly for ex vivo doses ranging from 50 to 35,000 Gy.

Radiation↗

Production of High Specific Activity 155 Tb, 161 Tb and 203 Pb for Research and Clinical Applications: Effective Target Design, Target Material Recycling and Radioisotope Separation (Final Technical Report)

The overall objectives of this project were (1) to develop methods for the production and separation of a diagnostic and therapeutic or “theranostic” pair of radioisotopes, terbium-155 ( 155 Tb) and terbium-161 ( 161 Tb) and (2) to train graduate students and postdoctoral fellows in technologies and methods used in radionuclide production. Radionuclides can be incorporated into drugs called radiopharmaceuticals that target a specific disease (e.g., cancer). The need for theranostic radionuclides is escalating with the clinical translation of radiopharmaceuticals due to their implementation in personalized medicine, which has demonstrated enhanced patient treatments. High purity and high specific activity radionuclides are critical for theranostic agent development, for example to maintain diagnostic image quality, to minimize radiation dose to the patient, and to increase uptake in the targeted tissue (e.g., tumor), especially in the case of receptor- and antigen-targeted agents. The 155 Tb (diagnostic) and 161 Tb (therapeutic) radioisotopes that were generated through this project are a theranostic pair with demonstrated potential for the development and translation into individualized, targeted, and dosimetry-driven radiotherapies. However, the development of such radiotherapies has been hindered by the lack of a routine and reliable supply of these isotopes in the United States. Methods for the production, separation, and supply of 155 Tb and 161 Tb were investigated and developed in this project. Further, the strong emphasis throughout the project on the training of graduate students and postdoctoral fellows has helped to ensure and enhance the nuclear science workforce through the training of the next generation of highly qualified scientists in nuclear and radiochemistry. This grant also continued a collaboration between scientists at the University of Washington (UW), the University of Missouri (MU) and Brookhaven National Laboratory (BNL). All three institutions were involved in the project, but to different degrees on the various tasks through which the overall objectives were met.

07 ISOTOPE AND RADIATION SOURCES↗

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response

Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy

Prostate bed (PB) irradiation is considered the standard postoperative treatment after radical prostatectomy (RP) for tumors with high-risk features or persistent prostate-specific antigen, or for salvage treatment in case of biological relapse. Four consensus guidelines have been published to standardize practices and reduce the interobserver variability in PB delineation but with discordant recommendations. To improve the reproducibility in the PB delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked to propose a new and more reproducible consensus guideline for PB clinical target volume (CTV) definition.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantification of Intrafraction and Interfraction Tumor Motion Amplitude and Prediction Error for Different Liver Tumor Trajectories in Cyberknife Synchrony Tracking

To research the fiducial-based, real-time tracking intrafraction (during the fraction [intra-]) and interfraction (between fractions [inter-]) tumor respiration amplitude, motion trajectory, and prediction error and quantify their relationships for different types of motion trajectories during Cyberknife-based stereotactic ablation radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dichloroacetate enhances the anti-tumor effect of sorafenib via modulating the ROS-JNK-Mcl-1 pathway in liver cancer cells

Liver cancer is one of the most common and high recurrence malignancies. Besides radiotherapy and surgery, chemotherapy also plays an essential role in the treatment of liver cancer. Sorafenib and sorafenib-based combination therapies have been proven efficacy against tumors. However, previous clinical studies have indicated that some patients with liver cancer are resistant to sorafenib treatment and the existing strategies are not satisfactory in the clinic. Therefore, it is urgent to investigate strategies to improve the effectiveness of sorafenib for liver cancer and to explore effective drug combinations. In the present study, we found that dichloroacetate (DCA) could significantly enhance the anti-tumor effect of sorafenib on liver cancer cells, including reduced viability and dramatically promoted apoptosis in liver cancer cells. Moreover, compared to sorafenib alone, the combination of DCA and sorafenib markedly increased the degradation of anti-apoptotic protein Mcl-1 by enhancing its phosphorylation. Overexpression of Mcl-1 could significantly attenuate the synergetic effect of DCA and sorafenib on apoptosis induction in liver cancer cells. Furthermore, we found that the ROS-JNK pathway was obviously activated in the DCA combined sorafenib group. The levels of ROS and p-JNK were dramatically up-regulated in the two drug combination groups. Antioxidant NAC could alleviate the synergetic effects of DCA and sorafenib on ROS generation, JNK activation, Mcl-1 degradation, and cell apoptosis. Moreover, DCA and sorafenib's effects on Mcl-1 degradation and apoptosis could also be inhibited by JNK inhibitor ‘SP’600125. Finally, the synergetic effects of DCA and sorafenib on tumor growth suppression, Mcl-1 degradation and induction of apoptosis were also validated in liver cancer xenograft in vivo. These findings indicate that DCA enhances the anti-tumor effect of sorafenib via the ROS-JNK-Mcl-1 pathway in liver cancer cells. This study may provide new insights to improve the chemotherapeutic effect of sorafenib, which may be benecial for further clinical application of sorafenib in liver cancer treatment.

60 APPLIED LIFE SCIENCES↗

Therapeutic targeting of membrane-associated proteins in central nervous system tumors

The activity of the most complex system, the central nervous system (CNS) is profoundly regulated by a huge number of membrane-associated proteins (MAP). A minor change stimulates immense chemical changes and the elicited response is organized by MAP, which acts as a receptor of that chemical or channel enabling the flow of ions. Slight changes in the activity or expression of these MAPs lead to severe consequences such as cognitive disorders, memory loss, or cancer. CNS tumors are heterogeneous in nature and hard-to-treat due to random mutations in MAPs; like as overexpression of EGFRvIII/TGFβR/VEGFR, change in adhesion molecules α5β3 integrin/SEMA3A, imbalance in ion channel proteins, etc. Extensive research is under process for developing new therapeutic approaches using these proteins such as targeted cytotoxic radiotherapy, drug-delivery, and prodrug activation, blocking of receptors like GluA1, developing viral vector against cell surface receptor. The combinatorial approach of these strategies along with the conventional one might be more potential. Henceforth, our review focuses on in-depth analysis regarding MAPs aiming for a better understanding for developing an efficient therapeutic approach for targeting CNS tumors.

60 APPLIED LIFE SCIENCES↗

Mast1 mediates radiation-induced gastric injury via the P38 MAPK pathway

Radiation-induced gastric injury is a serious adverse effect and reduces the efficacy of radiotherapy treatment. However, the mechanisms underlying radiation-induced stomach injury remain unclear. Here, mouse stomach and gastric epithelial cells were irradiated with different doses of X-ray radiation. The results showed that radiation induced gastric injury in vivo and in vitro. Differentially expressed functional mRNAs in irradiation-induced gastric tissues were screened from the Gene Expression Omnibus (GEO) database. We found that the expression of microtubule-associated serine/threonine kinase 1 (Mast1) was downregulated in mouse gastric tissues and gastric epithelial cells after irradiation. Furthermore, functional assays showed that knockdown of Mast1 inhibited growth and promoted apoptosis in gastric epithelial cells, while overexpression of Mast1 protected gastric epithelial cells from radiation damage. Mechanistically, Mast1 negatively regulated radiation-induced injury in gastric epithelial cells by inhibiting the activation of P38. The apoptosis caused by knockdown of Mast1 in gastric epithelial cells could be partially reversed by the P38 inhibitor SB203580. Moreover, data from several gastric cancer cell lines and online databases revealed that Mast1 was not involved in the development of gastric cancer. Collectively, our findings demonstrated that Mast1 is essential for radiation-induced gastric injury, providing a promising prognostic and therapeutic target.

60 APPLIED LIFE SCIENCES↗