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This study investigates how scattering foil materials and sampling holder placement affect electron energy distribution in electron beams from a modified medical linear accelerator for FLASH radiotherapy. We analyze electron energy spectra at various positions-ionization chamber, mirror, and jaw-to evaluate the impact of Cu, Pb-Cu, Pb, and Ta foils. Our findings show that close proximity to the source intensifies the dependence of electron energy distribution on foil material, enabling precise beam control through material selection. Monte Carlo simulations are effective for designing foils to achieve desired energy distributions. Moving the sampling holder farther from the source reduces foil material influence, promoting more uniform energy spreads, particularly in the 0.5-10 MeV range for 12 MeV electron beams. These insights emphasize the critical role of tailored material selection and sampling holder positioning in optimizing electron energy distribution and fluence intensity for FLASH radiotherapy research, benefiting both experimental design and clinical applications.
RESUMO
The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.
Assuntos
Neoplasias , Humanos , Neoplasias/radioterapia , Neoplasias/patologia , Neoplasias/metabolismo , Microambiente Tumoral/efeitos da radiação , Radioterapia/métodos , Animais , Espécies Reativas de Oxigênio/metabolismoRESUMO
Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as GafchromicTM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment.
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The dehydrocoupling of the fluorinated secondary phosphine-borane adduct R2PH.BH3 (R = p-CF3C6H4) at 60 degrees C is catalyzed by the rhodium complex [{Rh(mu-Cl)(1,5-cod)}2] to give the four-membered chain R2PH-BH2-R2P-BH3. A mixture of the cyclic trimer [R2P-BH2]3 and tetramer [R2P-BH2]4 was obtained from the same reaction at a more elevated temperature of 100 degrees C. The analogous rhodium-catalyzed dehydrocoupling of the primary phosphine-borane adduct RPH2.BH3 at 60 degrees C gave the high molecular weight polyphosphinoborane polymer [RPH-BH2]n (Mw = 56,170, PDI = 1.67). The molecular weight was investigated by gel permeation chromatography and the compound characterized by multinuclear NMR spectroscopy. Interestingly, the electron-withdrawing fluorinated aryl substituents have an important influence on the reactivity as the dehydrocoupling process occurred efficiently at the mildest temperatures observed for phosphine-borane adducts to date. Thin films of polymeric [RPH-BH2]n (R = p-CF3C6H4) have also been shown to function as effective negative-tone resists towards electron beam (e-beam) lithography (EBL). The resultant patterned bars were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS).
RESUMO
High molecular weight, soluble, air- and moisture-stable, highly metallized (>25 wt% metal) polyferrocenylsilanes (PFS) [Fe(eta-C5H4)2Si(Me){Co2(CO)6C2Ph}]n (Co-PFS), [Fe(eta-C5H4)2Si(Me){Mo2-Cp2(CO)4C2Ph}]n (Mo-PFS), and [Fe(eta-C5H4)2Si(Me){Ni2Cp2C2Ph}]n (Ni-PFS) containing pendant cobalt, molybdenum, and nickel clusters, respectively, have been prepared via macromolecular clusterization of an acetylide-substituted PFS [Fe(eta-C5H4)2Si(Me)C(triple bond)CPh]n with [Co(2)(CO)8], [{MoCp(CO)(2)}2], or [{NiCp(CO)}2]. The extent of clusterization achieved was in the range of 70-75%. All three highly metallized polymers were demonstrated to function as negative-tone resists in electron-beam lithography, while Co-PFS and Mo-PFS were successfully patterned by UV-photolithography, allowing the fabrication of micron-sized bars, dots, and lines. These studies suggest that the highly metallized polymers may be useful in the fabrication of patterned arrays of alloy nanoparticles for both materials science and catalytic applications.