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Boronated molecular systems can be applied to boron neutron capture therapy (BNCT). Among these systems, carborane‐containing phthalocyanines (Pcs) are the most promising BNCT agents. Herein we report the new zinc (II) complex of the hexacationic Pc 6, which has been obtained as iodide salt through quaternization of the neutral precursor with methyl iodide. Compound 6 was synthesized over a sequence of four steps. The complex, and its precursors as well, were characterized by a combination of spectroscopic techniques, and their structures assessed by 1H, 13C, 11B, and two‐dimensional NMR spectroscopy experiments. Together with a marked tendency to aggregate, 6 showed appreciable solubility in water. Singlet oxygen quantum yield (ΦΔ) of 0.38, and fluorescence quantum yield (ΦF) of 0.13 were obtained for 6 in a DMF solution. The complex proved to be very effective in enriching UMR‐106 cells with 10B, showing very good performance even in case of very low concentrations exposure, i. e. 1 ppm, that moreover resulted in a mild cytotoxic effect. Such a feature can be related to the polycationic nature of the complex, and hence to the well‐known propensity of positively charged species to enter the cellular membrane or to adhere to its external surface. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator.Methods: The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison.Results: The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy.Conclusions: The possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we propose a bottom-up approach to obtain new boron carriers built with ortho-carborane functionalized gold nanoparticles (GNPs) for applications in Boron Neutron Capture Therapy. The interaction between carboranes and the gold surface was assured by one or two SH-groups directly linked to the boron atoms of the B10C2 cage. This allowed obtaining stable, nontoxic systems, though optimal biological performance was hampered by low solubility in aqueous media. To improve cell uptake, the hydrophilic character of carborane functionalized GNPs was enhanced by further coverage with an appropriately tailored diblock copolymer (PEO-b-PCL). This polymer also contained pendant carboranes to provide anchoring to the pre-functionalized GNPs. In vitro tests, carried out on osteosarcoma cells, showed that the final vectors possessed excellent biocompatibility joint to the capacity of concentrating boron atoms in the target, which is encouraging evidenced to pursue applications in vivo. [Copyright &y& Elsevier]

26933390 4 Suzuki M. Boron neutron capture therapy (BNCT): A unique role in radiotherapy with a view to entering the accelerator-based BNCT era. Boron Neutron Capture Therapy (BNCT) is a binary radiation treatment exploiting a nuclear reaction occurring in tumor cells. More interconnections between standard photon therapy and charged particle therapy methods and BNCT should be fostered to establish a common language that can be used to compare and eventually combine treatments. [Extracted from the article]

Abstract: The possibility to measure boron concentration with high precision in tissues that will be irradiated represents a fundamental step for a safe and effective BNCT treatment. In Pavia, two techniques have been used for this purpose, a quantitative method based on charged particles spectrometry and a boron biodistribution imaging based on neutron autoradiography. A quantitative method to determine boron concentration by neutron autoradiography has been recently set-up and calibrated for the measurement of biological samples, both solid and liquid, in the frame of the feasibility study of BNCT. This technique was calibrated and the obtained results were cross checked with those of α spectrometry, in order to validate them. The comparisons were performed using tissues taken form animals treated with different boron administration protocols. Subsequently the quantitative neutron autoradiography was employed to measure osteosarcoma cell samples treated with BPA and with new boronated formulations. [Copyright &y& Elsevier]

Boron Neutron Capture Therapy (BNCT) is a radiotherapy technique based on the enrichment of tumour cells with suitable 10-boron concentration and on subsequent neutron irradiation. Low-energy neutron irradiation produces a localized deposition of radiation dose caused by boron neutron capture reactions. Boron is vehiculated into tumour cells via proper borated formulations, able to accumulate in the malignancy more than in normal tissues. The neutron capture releases two high-LET charged particles (i.e., an alpha particle and a lithium ion), losing their energy in a distance comparable to the average dimension of one cell. Thus BNCT is selective at the cell level and characterized by high biological effectiveness. As the radiation field is due to the interaction of neutrons with the components of biological tissues and with boron, the dosimetry requires a formalism to express the absorbed dose into photon-equivalent units. This work analyzes a clinical case of an adenoid cystic carcinoma treated with carbon-ion radiotherapy (CIRT), located close to optic nerve and deep-seated as a practical example of how to apply the formalism of BNCT photon isoeffective dose and how to evaluate the BNCT dose distribution against CIRT. The example allows presenting different dosimetrical and radiobiological quantities and drawing conclusions on the potential of BNCT stemming on the clinical result of the CIRT. The patient received CIRT with a dose constraint on the optic nerve, affecting the peripheral part of the Planning Target Volume (PTV). After the treatment, the tumour recurred in this low-dose region. BNCT was simulated for the primary tumour, with the goal to calculate the dose distribution in isoeffective units and a Tumour Control Probability (TCP) to be compared with the one of the original treatment. BNCT was then evaluated for the recurrence in the underdosed region which was not optimally covered by charged particles due to the proximity of the optic nerve. Finally, a combined treatment consisting in BNCT and carbon ion therapy was considered to show the consistency and the potential of the model. For the primary tumour, the photon isoeffective dose distribution due to BNCT was evaluated and the resulted TCP was higher than that obtained for the CIRT. The formalism produced values that are consistent with those of carbon-ion. For the recurrence, BNCT dosimetry produces a similar TCP than that of primary tumour. A combined treatment was finally simulated, showing a TCP comparable to the BNCT-alone with overall dosimetric advantage in the most peripheral parts of the treatment volume. Isoeffective dose formalism is a robust tool to analyze BNCT dosimetry and to compare it with the photon-equivalent dose calculated for carbon-ion treatment. This study introduces for the first time the possibility to combine the dosimetry obtained by two different treatment modalities, showing the potential of exploiting the cellular targeting of BNCT combined with the precision of charged particles in delivering an homogeneous dose distribution in deep-seated tumours. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a radiotherapy technique based on the enrichment of tumour cells with suitable 10-boron concentration and on subsequent neutron irradiation. Low-energy neutron irradiation produces a localized deposition of radiation dose caused by boron neutron capture reactions. Boron is vehiculated into tumour cells via proper borated formulations, able to accumulate in the malignancy more than in normal tissues. The neutron capture releases two high-LET charged particles (i.e., an alpha particle and a lithium ion), losing their energy in a distance comparable to the average dimension of one cell. Thus BNCT is selective at the cell level and characterized by high biological effectiveness. As the radiation field is due to the interaction of neutrons with the components of biological tissues and with boron, the dosimetry requires a formalism to express the absorbed dose into photon-equivalent units. This work analyzes a clinical case of an adenoid cystic carcinoma treated with carbon-ion radiotherapy (CIRT), located close to optic nerve and deep-seated as a practical example of how to apply the formalism of BNCT photon isoeffective dose and how to evaluate the BNCT dose distribution against CIRT. The example allows presenting different dosimetrical and radiobiological quantities and drawing conclusions on the potential of BNCT stemming on the clinical result of the CIRT. The patient received CIRT with a dose constraint on the optic nerve, affecting the peripheral part of the Planning Target Volume (PTV). After the treatment, the tumour recurred in this low-dose region. BNCT was simulated for the primary tumour, with the goal to calculate the dose distribution in isoeffective units and a Tumour Control Probability (TCP) to be compared with the one of the original treatment. BNCT was then evaluated for the recurrence in the underdosed region which was not optimally covered by charged particles due to the proximity of the optic nerve. Finally, a combined treatment consisting in BNCT and carbon ion therapy was considered to show the consistency and the potential of the model. For the primary tumour, the photon isoeffective dose distribution due to BNCT was evaluated and the resulted TCP was higher than that obtained for the CIRT. The formalism produced values that are consistent with those of carbon-ion. For the recurrence, BNCT dosimetry produces a similar TCP than that of primary tumour. A combined treatment was finally simulated, showing a TCP comparable to the BNCT-alone with overall dosimetric advantage in the most peripheral parts of the treatment volume. Isoeffective dose formalism is a robust tool to analyze BNCT dosimetry and to compare it with the photon-equivalent dose calculated for carbon-ion treatment. This study introduces for the first time the possibility to combine the dosimetry obtained by two different treatment modalities, showing the potential of exploiting the cellular targeting of BNCT combined with the precision of charged particles in delivering an homogeneous dose distribution in deep-seated tumours. [ABSTRACT FROM AUTHOR]

New multifunctional theranostic vectors allow the expansion of cancer therapeutic approaches toward scarcely investigated fields. One example is the combination of boron neutron capture therapy (BNCT) and X‐ray radiotherapy (XRT) for treating normal and XRT‐resistant hypoxic tumor regions and reduce recurrence. Of great relevance for BNCT is also the support of viable, rapid, safe, and reliable techniques for the localization and quantification of the radiosensitizers in the tissues. To address these challenges, polymer‐coated Au‐B nanoparticles (NPs) are obtained starting from a laser ablation in liquid process. Despite thermodynamic constraints, the two elements coexist by short‐range boron segregation in the gold lattice, as demonstrated experimentally and explained with the support of density functional theory calculations. Thus, the Au‐B NPs maintain a marked gold character such as biocompatibility, stability, and straightforward surface chemistry with thiolated compounds, desirable for the integration with agents capable of cell targeting and internalization. Overall, the Au‐B NPs exhibit the appropriate features for the investigation of combined BNCT and XRT, supported by the localization and quantification with X‐ray computed tomography imaging. Besides, the Au‐B nanotechnology tool is achievable without renouncing to reproducibility, environmental sustainability, and cost affordability thanks to the laser‐assisted synthetic pathway. [ABSTRACT FROM AUTHOR]

Neutron capture therapy (NCT) is a form of radiotherapy that exploits the potential of some specific isotopes to capture thermal neutrons and subsequently yield high linear energy transfer (LET) particles, suitable for cancer treatment. Recently, relevant technological improvements have been made in terms of accelerators as suitable neutron sources for NCT at hospitals. However, low selective delivery of current drugs to cancer cells remains as the main challenge for successful clinical application of NCT. This work presents an innovative and previously unexplored approach for the design of nanotherapeutic NCT agents. Herein, a new concept based on carbon nanomaterials that seal 6Li active NCT nuclides is investigated. The 6Li active species are located in the inner cavity of the nanocarrier (carbon nanohorns or carbon nanotubes) and therefore, completely protected from the biological environment, avoiding toxicity and degradation. After encapsulation of the active cargo, the external surface of the nanocarrier is modified for improved biocompatibility. The developed 6Li-filled carbon nanohorns offered the possibility to explore 6Li compounds as active NCT agents by delivering therapeutic doses to cancer cells. We envisage that nanoencapsulation of 6Li can trigger the successful development and implementation of Lithium Neutron Cancer Therapy (LiNCT). [Display omitted] [ABSTRACT FROM AUTHOR]

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a radiotherapy whose effect is due to the combination of low-energy neutron irradiation prior chemical targeting of tumour tissues with boron-10. The context of this work is the design of a clinical BNCT facility based on a Radio-Frequency Quadrupole proton accelerator, manufactured by the Italian National Institute of Nuclear Physics (INFN). Such a machine can provide a neutron beam suitable for the treatment of deep-seated tumours when coupled to a beryllium target and a Beam Shaping Assembly whose main constituent is densified lithiated aluminium fluoride. This paper refines the design of the facility, already addressed in preliminary studies, from the point of view of dosimetric quantities in the room and in the patient. The presented calculations have been performed with different Monte Carlo codes, and assess the time evolution of the dose due to the neutron activation of the irradiated materials. A comprehensive evaluation of the dose absorbed in the healthy organs of the patient is provided, with focus on the residual radioactivity of the patient urine, for three different treatment positions. Borated concrete is confirmed to be the best material for constructing the walls of the treatment room. A lead shielding at the beam-port is proposed to reduce the gamma dose at the irradiation position due to the activation of the Beam Shaping Assembly. • Calculations of activation and dosimetry help in designing the treatment room. • Radiation protection is pivotal for the design of a BNCT facility. • Borated concrete walls reduce the activation of tissues and urine. • Borated concrete walls reduce the ambient dose due the neutron activation. • A beamport shield decreases ambient dose due to materials activation. [ABSTRACT FROM AUTHOR]

Abstract: A PGNAA facility is being developed for 10B concentration measurements at RA-3 reactor. Its design targets detection limits better than tenths of a microgram and irradiation times on the order of minutes. Computational models were developed, which estimated thermal neutron fluxes in irradiation position to be larger than 109 ncm−2 s−1. Calculated amounts of photons and fast neutrons make necessary for filter/moderator arrangements. An irradiation device was designed and numerically tested, which is being built and is to be used for performing characterizing measurements. [Copyright &y& Elsevier]

This paper aims to investigate how the spatial distribution of boron in cells and oxygen concentration affect the DNA damage induced by charged particles in boron neutron capture therapy (BNCT) by Monte Carlo simulations, and further to evaluate the relative biological effectiveness (RBE) of DNA double-strand breaks (DSBs) induction. The kinetic energy spectra of α, 7Li particles in BNCT arriving at the nucleus surface were obtained from GEANT4 (Geant4 10.05.p01). The DNA damage caused by BNCT was then evaluated using MCDS (MCDS 3.10A). When α or 7Li particles were distributed in the cytomembrane or cytoplasm, the difference in DNA damage of the same types was less than 0.5%. Taking the 137Cs photons as the reference radiation, when the oxygen concentration varied from 0% to 50%, the RBE of 0.54MeV protons and recoil protons varied from 5 to 2, whereas it decreased from 10 to 3 for α or 7Li particles. The RBE of DSB induction all charged particles in BNCT decreased with the increase of oxygen concentration. This work indicated that the RBE of different radiation particles of BNCT might be affected by many factors, which should be paid attention to in theoretical research or clinical application. [ABSTRACT FROM AUTHOR]

Purpose: Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. BNCT has been proposed for the treatment of multiple, non-resectable, diffuse tumors in lung. The aim of the present study was to evaluate the therapeutic efficacy and toxicity of BNCT in an experimental model of lung metastases of colon carcinoma in BDIX rats and perform complementary survival studies. Materials and methods: We evaluated tumor control and toxicity in lung 2 weeks post-BNCT at 2 dose levels, including 5 experimental groups per dose level: T0 (euthanized pre-treatment), Boronophenylalanine-BNCT (BPA-BNCT), BPA + Sodium decahydrodecaborate-BNCT ((BPA + GB-10)-BNCT), Beam only (BO) and Sham (no treatment, same manipulation). Tumor response was assessed employing macroscopic and microscopic end-points. An additional experiment was performed to evaluate survival and oxygen saturation in blood. Results and conclusions: No dose-limiting signs of short/medium-term toxicity were observed in lung. All end-points revealed statistically significant BNCT-induced tumor control vs Sham at both dose levels. The survival experiment showed a statistically significant 45% increase in post-treatment survival time in the BNCT group (48 days) versus Sham (33 days). These data consistently revealed growth suppression of lung metastases by BNCT with no manifest lung toxicity. Boron Neutron Capture Therapy suppresses growth of experimental lung metastases No BNCT-induced short/medium-term toxicity in lung is associated with tumor control Boron Neutron Capture Therapy increased post-treatment survival time by 45% [ABSTRACT FROM AUTHOR]

The neutron autoradiography technique using polycarbonate nuclear track detectors (NTD) has been extended to quantify the boron concentration in hard tissues, an application of special interest in Boron Neutron Capture Therapy (BNCT). Chemical and mechanical processing methods to prepare thin tissue sections as required by this technique have been explored. Four different decalcification methods governed by slow and fast kinetics were tested in boron-loaded bones. Due to the significant loss of the boron content, this technique was discarded. On the contrary, mechanical manipulation to obtain bone powder and tissue sections of tens of microns thick proved reproducible and suitable, ensuring a proper conservation of the boron content in the samples. A calibration curve that relates the 10 B concentration of a bone sample and the track density in a Lexan NTD is presented. Bone powder embedded in boric acid solution with known boron concentrations between 0 and 100 ppm was used as a standard material. The samples, contained in slim Lexan cases, were exposed to a neutron fluence of 10 12 cm −2 at the thermal column central facility of the RA-3 reactor (Argentina). The revealed tracks in the NTD were counted with an image processing software. The effect of track overlapping was studied and corresponding corrections were implemented in the presented calibration curve. Stochastic simulations of the track densities produced by the products of the 10 B thermal neutron capture reaction for different boron concentrations in bone were performed and compared with the experimental results. The remarkable agreement between the two curves suggested the suitability of the obtained experimental calibration curve. This neutron autoradiography technique was finally applied to determine the boron concentration in pulverized and compact bone samples coming from a sheep experimental model. The obtained results for both type of samples agreed with boron measurements carried out by ICP-OES within experimental uncertainties. The fact that the histological structure of bone sections remains preserved allows for future boron microdistribution analysis. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop an innovative imaging guided approach based on Boron Neutron Capture Therapy, for the treatment of mesothelioma, assisted by the quantification of the in vivo boron distribution by MRI. The herein reported results demonstrate that overexpressed Low Density Lipoproteins receptors can be successfully exploited to deliver to mesothelioma cells a therapeutic dose of boron (26 μg/g), significantly higher than in the surrounding tissue (3.5 μg/g). Boron and Gd cells uptake was assessed by ICP-MS and MRI on two mesothelioma (ZL34, AE17) and two healthy (MRC-5 and NMuMg) cell lines. An in vivo model was prepared by subcutaneous injection of ZL34 cells in Nu/Nu mice. After irradiation with thermal neutrons, tumor growth was evaluated for 40 days by MRI. Tumor masses of boron treated mice showed a drastic reduction of about 80–85%. The obtained results appear very promising providing patients affected by this rare disease with an improved therapeutic option, exploiting LDL transporters. [ABSTRACT FROM AUTHOR]

An inter-comparison of three boron determination techniques was carried out between laboratories from INFN-University of Pavia (Italy) and CNEA (Argentina): alpha spectrometry (alpha-spect), neutron capture radiography (NCR) and quantitative autoradiography (QTA). Samples of different nature were analysed: liquid standards, liver homogenates and tissue samples from different treatment protocols. The techniques showed a good agreement in a concentration range of interest in BNCT (1–100 ppm), thus demonstrating their applicability as precise methods to quantify boron and determine its distribution in tissues. [ABSTRACT FROM AUTHOR]

An inter-comparison of three boron determination techniques was carried out between laboratories from INFN-University of Pavia (Italy) and CNEA (Argentina): alpha spectrometry (alpha-spect), neutron capture radiography (NCR) and quantitative autoradiography (QTA). Samples of different nature were analysed: liquid standards, liver homogenates and tissue samples from different treatment protocols. The techniques showed a good agreement in a concentration range of interest in BNCT (1–100 ppm), thus demonstrating their applicability as precise methods to quantify boron and determine its distribution in tissues. [ABSTRACT FROM AUTHOR]

The zinc(ii) complex of the octa-anionic 2,3,9,10,16,17,23,24-octakis-(7-methyl-7,8-dicarba-nido-undeca-boran-8-yl)hexyl-thio-6,13,20,27-phthalocyanine (nido-[ZnMCHESPc]Cs8, 7) has been obtained in the form of caesium salt through mild deboronation of the neutral precursor, the closo-[ZnMCHESPc] complex, 6, with CsF. 6 has been synthesized, in turn, by heating a finely ground mixture of the appropriate phthalonitrile and zinc(ii) acetate at 180.0 °C. The complexes have been characterized by elemental analyses, FT-IR, UV-visible absorption and fluorescence emission spectroscopy, and their structures were assessed by 1H, 13C, 11B, and two-dimensional homo- and hetero-correlated NMR spectroscopy experiments. 7 showed appreciable solubility in water solution, together with a marked tendency to aggregate. Aggregation of 7 in the hydrotropic medium resulted in significant fluorescence quenching. Instead, fluorescence quantum yields (ΦF) of 0.14 and 0.08, and singlet oxygen quantum yields (ΦΔ) of 0.63 and 0.24 were obtained for 6 and 7, respectively, in a DMF solution. In vitro boron neutron capture therapy (BNCT) experiments, employing boron imaging techniques as implemented in qualitative and quantitative neutron autoradiography methods, showed that 7 is capable of increasing the boron concentration of two selected cancerous cell lines, the DHD/K12/TRb of rat colon adenocarcinoma and UMR-106 of rat osteosarcoma, with the large-size Cs+ counter-ions used to neutralize the negatively charged carborane polyhedra not presenting a significant obstacle to the process. Taken together, BNCT and photophysical measurement results indicated that 7 is potentially suitable for bimodal or multimodal anticancer therapy. [ABSTRACT FROM AUTHOR]

Background. We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Material and Methods. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Results. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Conclusion. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control. [ABSTRACT FROM AUTHOR]

Advances in neutron-based radiation therapies such as Boron Neutron Capture Therapy (BNCT) pushes towards the development of new neutron spectrometers, whose key features are to be their practicability, reliability, energy resolution and detection range. The ACSpect is a novel neutron spectrometer based on a two-stages monolithic silicon telescope detector coupled to an organic scintillator working as an active neutron converter. This paper reports the latest developments of the ACSpect and the results of the measurements of an accelerator-based neutron beam moderated by A l F 3. The A l F 3 is a moderator material optimised to obtain an epithermal neutron beam for accelerator-based BNCT of deep seated tumours. The experiments carried out are the first neutron spectrometry of a neutron beam moderated by A l F 3. The performances of the ACSpect have been compared against Monte Carlo simulations, literature data and the gold-standard neutron spectrometer DIAMON. While the agreement between experiments and simulations allowed to validate the Monte Carlo model used to simulate the new moderator material, the agreement between literature data, ACSpect and DIAMON results confirmed the ACSpect as a compact and relatively easy-to-use high-resolution neutron spectrometer, capable of reliably operating in the energy range 250 keV - 4 MeV. • Improvement of the ACSpect high-resolution neutron spectrometer. • Performances of the ACSpect against a 5 MeV protons Be(p,n)B neutron field. • First measurements of a neutron beam moderated by A l F 3 for BNCT application. • Validation of MCNP6 simulations of a neutron beam moderated by A l F 3 [ABSTRACT FROM AUTHOR]

Abstract: The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that 18F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose–boronophenylalanine (BPA). Therefore, FET–PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT. [Copyright &y& Elsevier]

Abstract: The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. [Copyright &y& Elsevier]

Simple Summary: A compact neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. The source comprises an original design tandem accelerator, solid lithium target, and a neutron beam shaping assembly. The neutron source is capable of producing the high neutron flux in various energy ranges, from thermal to fast, for boron neutron capture therapy, as well as for other applications. A lot of scientific research has been carried out at the facility, including the study of blistering and its effect on the neutron yield. The Boron Neutron Capture Therapy (BNCT) technique is being tested in in vitro and in vivo studies, and the methods of dosimetry are being developed. It is planned to certify the neutron source next year and conduct clinical trials on it. The neutron source served as a prototype for a facility created for a clinic in Xiamen (China). A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The proton beam energy can be varied within a range of 0.6–2.3 MeV, keeping a high-energy stability of 0.1%. The beam current can also be varied in a wide range (from 0.3 mA to 10 mA) with high current stability (0.4%). In the device, neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction. A beam-shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. A lot of scientific research has been carried out at the facility, including the study of blistering and its effect on the neutron yield. The BNCT technique is being tested in in vitro and in vivo studies, and the methods of dosimetry are being developed. It is planned to certify the neutron source next year and conduct clinical trials on it. The neutron source served as a prototype for a facility created for a clinic in Xiamen (China). [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical potential and safety are presented as novel criteria to evaluate neutron beams designed for boron neutron capture therapy (BNCT). The presently used figures of merit are a set of physical quantities calculated in air, related to the neutron flux, the collimation, and the spectral characteristics. However, the capability of the beam to deliver an effective and safe treatment to patients should be the most important criterion in view of the clinical application. This work presents the design of a neutron beam produced by a proton accelerator coupled to a beryllium target and the use of new figures of merit to choose the best beam among different candidates. These figures of merit use tridimensional dosimetry simulated in phantoms and patients, to calculate the probability of tumor control without affecting healthy tissues, employing proper radiobiological models. Moreover, the dose absorbed by out-of-field healthy organs is used as a criterion to establish the safest beam for clinical treatments. Results show that beams that would be rejected by physical in-air quantities demonstrate a clinical performance comparable to existing neutron beams successfully used for patients, and that the presented criteria allow a clear selection of the most adequate beam among the ones presented. (1) Background:The quality of neutron beams for Boron Neutron Capture Therapy (BNCT) is currently defined by its physical characteristics in air. Recommendations exist to define whether a designed beam is useful for clinical treatment. This work presents a new way to evaluate neutron beams based on their clinical performance and on their safety, employing radiobiological quantities. (2) Methods: The case study is a neutron beam for deep-seated tumors from a 5 MeV proton beam coupled to a beryllium target. Physical Figures of Merit were used to design five beams; however, they did not allow a clear ranking of their quality in terms of therapeutic potential. The latter was then evaluated based on in-phantom dose distributions and on the calculation of the Uncomplicated Tumor Control Probability (UTCP). The safety of the beams was also evaluated calculating the in-patient out-of-beam dosimetry. (3) Results: All the beams ensured a UTCP comparable to the one of a clinical beam in phantom; the safety criterion allowed to choose the best candidate. When this was tested in the treatment planning of a real patient treated in Finland, the UTCP was still comparable to the one of the clinical beam. (4) Conclusions: Even when standard physical recommendations are not met, radiobiological and dosimetric criteria demonstrate to be a valid tool to select an effective and safe beam for patient treatment. [ABSTRACT FROM AUTHOR]

In Boron Neutron Capture Therapy, the boronated drug plays a leading role in delivering a lethal dose to the tumour. The effectiveness depends on the boron macroscopic concentration and on its distribution at sub-cellular level. This work shows a way to colocalize alpha particles and lithium ions tracks with cells. A neutron autoradiography technique is used, which combines images of cells with images of tracks produced in a solid-state nuclear track detector. • Overlay of tracks from the 10B (n,α)7Li reaction over cells. • An affordable technique to study newly formulated 10B drugs. • Cells can be seeded directly on a CR39. • High resolution autoradiography limited by track diameter of ≈ 1 μm. [ABSTRACT FROM AUTHOR]

Preliminary studies for the design of an accelerator-based BNCT clinical facility are presented. The Beam Shaping Assembly neutron activation was evaluated experimentally and with Monte Carlo simulations. The activations of patient, air and walls in the room, the absorbed doses by the patient and the in-air dose distributions were evaluated. Based on these calculations, different walls compositions were tested to optimize the environmental conditions. Borated concrete, advantageously reducing the thermal flux in the room, was proven the best choice. • Radiation protection in Boron Neutron Capture Therapy facilities is crucial. • Preliminary studies for a facility with a high-intensity epithermal neutron beam. • Evaluation of neutron activations of Beam Shaping Assembly, air and patient. • Calculation of dose distributions in the room air and in the patient healthy organs. • Boron-loaded concrete helpfully reduces dosimetry and activations. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the cancers with high morbidity and mortality. Boron neutron capture therapy (BNCT) has attracted researchers' attention in recent years because of its unique advantages in lung cancer treatment. However, changes in dose distribution in BNCT due to respiratory motion have not been studied. In this work, the tumor dose deviation caused by respiration was quantitatively investigated. Four-dimensional Computed Tomography (4D CT) was used to construct the virtual respiratory patient model in this study. Six phases (e.g., 10%, 20%, 50%, 60%, 80%, and 90%) were selected to represent the anatomy of patients at different moments throughout the respiratory cycle. Tumor-related dose volume histograms (DVH) indices at different phases were calculated using Monte Carlo toolkit. The results showed that the dose difference increased with the increasing of respiratory motion amplitude. In the three movement directions of the tumor, the dose changes caused by the movement in the anterior–posterior (AP) direction were remarkable under the treatment planning configurations we studied. The differences of tumor mean dose ranged from −13.8% to 15.8%. Similar conclusions were observed in the cases of three real patients. • 4D CT was used to construct the patients geometry for dose calculation. • Dose differences increased with the increasing of respiratory motion amplitude. • The motion parallel to the irradiation direction contributed most to dose changes. [ABSTRACT FROM AUTHOR]