Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.
- MeSH
- bor chemie MeSH
- glioblastom radioterapie farmakoterapie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty radioterapie farmakoterapie MeSH
- protonová terapie * metody MeSH
- protony MeSH
- terapie metodou neutronového záchytu (bor-10) * metody MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Ultra-short electron beams are used as ultra-fast radiation source for radiobiology experiments aiming at very high energy electron beams (VHEE) radiotherapy with very high dose rates. Laser plasma accelerators are capable of producing electron beams as short as 1 fs and with tunable energy from few MeV up to multi-GeV with compact footprint. This makes them an attractive source for applications in different fields, where the ultra-short (fs) duration plays an important role. The time dynamics of the dose deposited by electron beams with energies in the range 50-250 MeV have been studied and the results are presented here. The results set a quantitative limit to the maximum dose rate at which the electron beams can impart dose.
- Klíčová slova
- flash radioterapie,
- MeSH
- ionizující záření MeSH
- lidé MeSH
- nádory terapie MeSH
- radioterapie * klasifikace metody MeSH
- vysokoenergetická radioterapie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Proton radiotherapy for the treatment of cancer offers an excellent dose distribution. Cellular experiments have shown that in terms of biological effects, the sharp dose distribution is further amplified, by as much as 75%, in the presence of boron. It is a matter of debate whether the underlying physical processes involve the nuclear reaction of 11B with protons or 10B with secondary neutrons, both producing densely ionizing short-ranged particles. Likewise, potential roles of intercellular communication or boron acting as a radiosensitizer are not clear. We present an ongoing research project based on a multiscale approach to elucidate the mechanism by which boron enhances the effectiveness of proton irradiation in the Bragg peak. It combines experimental with simulation tools to study the physics of proton-boron interactions, and to analyze intra- and inter-cellular boron biology upon proton irradiation.
Boron derivatives have great potential in cancer diagnostics and treatment. Borocaptates are used in boron neutron capture therapy and potentially in proton boron fusion therapy. This work examines modulation effects of two borocaptate compounds on radiation-induced DNA damage. Aqueous solutions of pBR322 plasmid containing increasing concentrations of borocaptates were irradiated with 60Co gamma rays or 30 MeV protons. Induction of single and double DNA strand breaks was investigated using agarose gel electrophoresis. In this model system, representing DNA without the intervention of cellular repair mechanisms, the boron derivatives acted as antioxidants. Clinically relevant boron concentrations of 40 ppm reduced the DNA single strand breakage seven-fold. Possible mechanisms of the observed effect are discussed.
UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.
The most important dosimetry quantity that is determined at radiotherapy centers is the absorbed dose to water for external beams. Fixed tolerances for absorbed doses measured under reference conditions with an ionization chamber for high-energy photon and electron beams are usually 2 and 3%, respectively, regardless of uncertainties of the input variables and other conditions during evaluation. In reality, this agreement should be evaluated considering the uncertainties of the input variables because they affect the size of the random deviations of the measurements from their true values. The aim of this work was to develop a new approach to evaluate the agreement between measured and reported values based on statistical interference rather than to use fixed tolerance levels. The proposed method considers different scenarios that can occur during the evaluation of agreement. Because the method is described in general, it can be used in all similar situations when partial uncertainties can be established.
- MeSH
- celková dávka radioterapie MeSH
- kalibrace MeSH
- lidé MeSH
- nádory radioterapie MeSH
- nejistota MeSH
- plánování radioterapie pomocí počítače metody normy MeSH
- radioterapie s modulovanou intenzitou metody normy MeSH
- statistické modely * MeSH
- vysokoenergetická radioterapie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this review was to define appropriate 11B delivery agents for boron proton-capture enhanced proton therapy (BPCEPT) taking into account the accumulated knowledge on boron compounds used for boron neutron capture therapy (BNCT). BPCEPT is a promising treatment approach which uses a high linear energy transfer (LET) dose component in conjunction with conventional proton therapy to increase the relative biological effectiveness of highly-selective charged particle therapy. Boron proton fusion reactions occur with highest cross section at certain proton energy level and thus can be tailored to the target volume with careful treatment planning that defines the 675 MeV proton distribution with high accuracy. Appropriate 11B compounds are required in order to achieve relevant high LET dose contribution from the boron proton-capture reaction. Previous scientific results and experiences with BNCT provide background knowledge and information regarding the optimization of boronated compound development, their characterization, measurement and imaging. However, there are substantial differences between BNCT and BPCEPT, which in turn places special unique chemical, physical and biological demands on 11B-carrier compounds for BPCEPT. In this review, we evaluate well-known and recently developed boron compounds for BPCEPT.
Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.
- MeSH
- alfa částice terapeutické užití MeSH
- bor chemie terapeutické užití MeSH
- borohydridy chemie MeSH
- buněčná smrt účinky záření MeSH
- chromozomální aberace účinky záření MeSH
- cyklotrony MeSH
- DNA nádorová genetika metabolismus účinky záření MeSH
- fluorescenční barviva chemie MeSH
- izotopy uhlíku chemie MeSH
- karyotypizace MeSH
- kombinovaná terapie přístrojové vybavení metody MeSH
- lidé MeSH
- lineární přenos energie MeSH
- nádorové buněčné linie MeSH
- nádory prostaty patologie radioterapie MeSH
- neutrony * MeSH
- poškození DNA MeSH
- protonová terapie * přístrojové vybavení metody MeSH
- relativní biologická účinnost MeSH
- sulfhydrylové sloučeniny chemie MeSH
- terapie metodou neutronového záchytu (bor-10) přístrojové vybavení metody MeSH
- vztah dávky záření a odpovědi MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
