Charged particle spectrometry to measure 10B concentration in bone.

Osteosarcoma is the most common primary malignant tumour of bone in young patients. The survival of these patients has largely been improved due to adjuvant and neo-adjuvant chemotherapy in addition to surgery. Boron neutron capture therapy (BNCT) is proposed as a complementary therapy, due to its ability to inactivate tumour cells that may survive the standard treatment and that may be responsible for recurrences and/or metastases. BNCT is based on neutron irradiation of a tumour enriched in 10B with a boron-loaded drug. Low-energy neutron capture in 10B creates charged particles that impart a high dose to tumour cells, which can be calculated only knowing the boron concentration. Charged particle spectrometry is a method that can be used to quantify boron concentration. This method requires acquisition of the energy spectra of charged particles such as alpha particles produced by neutron capture reactions in thin tissue sections irradiated with low-energy neutrons. Boron concentration is then determined knowing the stopping power of the alpha particles in the sample material. This paper describes the adaptation of this method for bone, with emphasis on sample preparation, experimental set-up and stopping power assessment of the involved alpha particles. The knowledge of boron concentration in healthy bones is important, because it allows for any dose limitation that might be necessary to avoid adverse effects such as bone fragility. The measurement process was studied through Monte Carlo simulations and analytical calculations. Finally, the boron content of bone samples was measured by alpha spectrometry at the TRIGA reactor in Pavia, Italy, and compared to that obtained by neutron autoradiography. The agreement between the results obtained with these techniques confirms the suitability of alpha spectrometry to measure boron in bone.

Assessment of long-term risks of secondary cancer in paediatric patients with brain tumours after boron neutron capture therapy.

This study firstly explored the risks of secondary cancer in healthy organs of Chinese paediatric patients with brain tumours after boron neutron capture therapy (BNCT). Three neutron beam irradiation geometries (i.e. right lateral, top to bottom, posterior to anterior) were adopted in treating patients with brain tumours under the clinical environment of BNCT. The concerned organs in this study were those with high cancer morbidity in China (e.g. lung, liver and stomach). The equivalent doses for these organs were calculated using Monte Carlo and anthropomorphic paediatric phantoms with Chinese physiological features. The risk of secondary cancer, characterised by the lifetime attributable risk (LAR) factor given in the BEIR VII report, was compared among the three irradiation geometries. The results showed that the LAR was lower with the PA irradiation geometry than with the two other irradiation geometries when the 2 cm diameter tumour was at a depth of 6 cm on the right side of the brain. Under the PA irradiation geometry, the LAR in the organs increased with increasing tumour volume and depth because of the long irradiation time. As the patients aged from 10-15 years old, the LAR decreased, which was related to the increased patient height and shortened life expectancy. Female patients had a relatively higher risk of secondary cancer than male patients in this study, which could be due to the thinner body thickness and the weaker protective effect on the internal organs of the female patients. In conclusion, the risks of secondary cancer in organs were related to irradiation geometries, gender, and age, indicating that the risk of secondary cancer is a personalised parameter that needs to be evaluated before administering BNCT, especially in patients with large or deep tumours.

An improved neutron autoradiography set-up for (10)B concentration measurements in biological samples.

AIM: Boron Neutron Capture Therapy (BNCT) is a binary hadrontherapy which exploits the neutron capture reaction in boron, together with a selective uptake of boronated substances by the neoplastic tissue. There is increasing evidence that future improvements in clinical BNCT will be triggered by the discovery of new boronated compounds, with higher selectivity for the tumor with respect to clinically used sodium borocaptate (BSH) and boronophenylalanine (BPA). BACKGROUND: Therefore, a (10)B quantification technique for biological samples is needed in order to evaluate the performance of new boronated formulations. MATERIALS AND METHODS: This article describes an improved neutron autoradiography set-up employing radiation sensitive films where the latent tracks are made visible by proper etching conditions. RESULTS: Calibration curves for both liquid and tissue samples were obtained. CONCLUSIONS: The obtained calibration curves were adopted to set-up a mechanism to point out boron concentration in the whole sample.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

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.

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation.

Synthesis of a carborane-containing cholesterol derivative and evaluation as a potential dual agent for MRI/BNCT applications.

In this study the synthesis and characterization of a new dual, imaging and therapeutic, agent is proposed with the aim of improving the efficacy of Boron Neutron Capture Therapy (BNCT) in cancer treatment. The agent (Gd-B-AC01) consists of a carborane unit (ten boron atoms) bearing a cholesterol unit on one side (to pursue the incorporation into the liposome bi-layer) and a Gd(iii)/1,4,7,10-tetraazacyclododecane monoamide complex on the other side (as a MRI reporter to attain the quantification of the B/Gd concentration). In order to endow the BNCT agent with specific delivery properties, the liposome embedded with the MRI/BNCT dual probes has been functionalized with a pegylated phospholipid containing a folic acid residue at the end of the PEG chain. The vector allows the binding of the liposome to folate receptors that are overexpressed in many tumor types, and in particular, in human ovarian cancer cells (IGROV-1). An in vitro test on IGROV-1 cells demonstrated that Gd-B-AC01 loaded liposomes are efficient carriers for the delivery of the MRI/BNCT probes to the tumor cells. Finally, the BNCT treatment of IGROV-1 cells showed that the number of surviving cells was markedly smaller when the cells were irradiated after internalization of the folate-targeted GdB10-AC01/liposomes.

The BIANCA model/code of radiation-induced cell death: application to human cells exposed to different radiation types.

This paper presents a biophysical model of radiation-induced cell death, implemented as a Monte Carlo code called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), based on the assumption that some chromosome aberrations (dicentrics, rings, and large deletions, called ''lethal aberrations'') lead to clonogenic inactivation. In turn, chromosome aberrations are assumed to derive from clustered, and thus severe, DNA lesions (called ''cluster lesions,'' or CL) interacting at the micrometer scale; the CL yield and the threshold distance governing CL interaction are the only model parameters. After a pilot study on V79 hamster cells exposed to protons and carbon ions, in the present work the model was extended and applied to AG1522 human cells exposed to photons, He ions, and heavier ions including carbon and neon. The agreement with experimental survival data taken from the literature supported the assumptions. In particular, the inactivation of AG1522 cells was explained by lethal aberrations not only for X-rays, as already reported by others, but also for the aforementioned radiation types. Furthermore, the results are consistent with the hypothesis that the critical initial lesions leading to cell death are DNA cluster lesions having yields in the order of *2 CL Gy-1 cell-1 at low LET and*20 CL Gy-1 cell-1 at high LET, and that the processing of these lesions is modulated by proximity effects at the micrometer scale related to interphase chromatin organization. The model was then applied to calculate the fraction of inactivated cells, as well as the yields of lethal aberrations and cluster lesions, as a function of LET; the results showed a maximum around 130 keV/lm, and such maximum was much higher for cluster lesions and lethal aberrations than for cell inactivation.

Using the photon isoeffective dose formalism to compare and combine BNCT and CIRT in a head and neck tumour.

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.

Combined BNCT-CIRT treatment planning for glioblastoma using the effect-based optimization.

Objective. Boron neutron capture therapy (BNCT) and carbon ion radiotherapy (CIRT) are emerging treatment modalities for glioblastoma. In this study, we investigated the methodology and feasibility to combine BNCT and CIRT treatments. The combined treatment plan illustrated how the synergistic utilization of BNCT's biological targeting and CIRT's intensity modulation capabilities could lead to optimized treatment outcomes.Approach. The Monte Carlo toolkit, TOPAS, was employed to calculate the dose distribution for BNCT, while matRad was utilized for the optimization of CIRT. The biological effect-based approach, instead of the dose-based approach, was adopted to develop the combined BNCT-CIRT treatment plans for six patients diagnosed with glioblastoma, considering the different radiosensitivity and fraction. Five optional combined treatment plans with specific BNCT effect proportions for each patient were evaluated to identify the optimal treatment that minimizes damage on normal tissue.Main results. Individual BNCT exhibits a significant effect gradient along with the beam direction in the large tumor, while combined BNCT-CIRT treatments can achieve uniform effect delivery within the clinical target volume (CTV) through the effect filling with reversed gradient by the CIRT part. In addition, the increasing BNCT effect proportion in combined treatments can reduce damage in the normal brain tissue near the CTV. Besides, the combined treatments effectively minimize damage to the skin compared to individual BNCT treatments.Significance. The initial endeavor to combine BNCT and CIRT treatment plans is achieved by the effect-based optimization. The observed advantages of the combined treatment suggest its potential applicability for tumors characterized by pleomorphic, infiltrative, radioresistant and voluminous features.

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications.

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.

3D bioprinted osteosarcoma model for experimental boron neutron capture therapy (BNCT) applications: Preliminary assessment.

Osteosarcoma is the most frequently primary malignant bone tumor characterized by infiltrative growth responsible for relapses and metastases. Treatment options are limited, and a new therapeutic option is required. Boron neutron capture therapy (BNCT) is an experimental alternative radiotherapy able to kill infiltrative tumor cells spearing surrounding healthy tissues. BNCT studies are performed on 2D in vitro models that are not able to reproduce pathological tumor tissue organization or on in vivo animal models that are expensive, time-consuming and must follow the 3R's principles. A 3D in vitro model is a solution to better recapitulate the complexity of solid tumors meanwhile limiting the animal's use. Objective of this study is to optimize the technical assessment for developing a 3D in vitro osteosarcoma model as a platform for BNCT studies: printing protocol, biomaterial selection, cell density, and crosslinking process. The best parameters that allow a fully colonized 3D bioprinted construct by rat osteosarcoma cell line UMR-106 are 6 × 106 cells/ml of hydrogel and 1% CaCl2 as a crosslinking agent. The proposed model could be an alternative or a parallel approach to 2D in vitro culture and in vivo animal models for BNCT experimental study.

Comparison of Photon Isoeffective Dose Models Based on In Vitro and In Vivo Radiobiological Experiments for Head and Neck Cancer Treated with BNCT.

Boron neutron capture therapy (BNCT) is a treatment modality for cancer that involves radiations of different qualities. A formalism that proved suitable to compute doses in photon-equivalent units is the photon isoeffective dose model. This study addresses the question whether considering in vitro or in vivo radiobiological studies to determine the parameters involved in photon isoeffective dose calculations affects the consistency of the model predictions. The analysis is focused on head and neck squamous cell carcinomas (HNSCC), a main target that proved to respond to BNCT. The photon isoeffective dose model for HNSCC with parameters from in vitro studies using the primary human cell line UT-SCC-16A was introduced and compared to the one previously reported with parameters from an in vivo oral cancer model in rodents. Both models were first compared in a simple scenario by means of tumor dose and control probability calculations. Then, the clinical impact of the different dose models was assessed from the analysis of a group of squamous cell carcinomas (SCC) patients treated with BNCT. Traditional dose calculations using the relative biological effectiveness factors derived from the SCC cell line were also analyzed. Predictions of tumor control from the evaluated models were compared to the patients' outcome. The quantification of the biological effectiveness of the different radiations revealed that relative biological effectiveness/compound biological effectiveness (RBE/CBE) factors for the SCC cell line are up to 20% higher than those assumed in clinical BNCT, highlighting the importance of using experimental data intimately linked to the tumor type to derive the model's parameters. The comparison of the different models showed that photon isoeffective doses based on in vitro data are generally greater than those from in vivo data (∼8-16% for total tumor absorbed doses of 10-15 Gy). However, the predictive power of the two models was not affected by these differences: both models fulfilled conditions to guarantee a good predictive performance and gave predictions statistically compatible with the clinical outcome. On the other hand, doses computed with the traditional model were substantially larger than those obtained with both photon isoeffective models. Moreover, the traditional model is statistically rejected, which reinforces the assertion that its inconsistencies are intrinsic and not due to the use of RBE/CBE factors obtained for a tumor type different from HN cancer. The results suggest that the nature of the radiobiological data would not affect the consistency of the photon isoeffective dose model in the studied cases of SCC head and neck cancer treated with BPA-based BNCT.

Multimodal evaluation of 19F-BPA internalization in pancreatic cancer cells for boron capture and proton therapy potential applications.

PURPOSE: One of the obstacles to the application of Boron Neutron Capture Therapy (BNCT) and Proton Boron Fusion Therapy (PBFT) concerns the measurement of borated carriers' biodistribution. The objective of the present study was to evaluate the in vitro internalization of the 19F-labelled p-boronophenylalanine (19F-BPA) in the human cancer pancreatic cell line (PANC-1) for the potential application of BNCT and PBFT in pancreatic cancer. The 19F-BPA carrier has the advantage that its bio-distribution may be monitored in vivo using 19F-Nuclear Magnetic Resonance (19F NMR). MATERIALS AND METHODS: The 19F-BPA internalization in PANC-1 cells was evaluated using three independent techniques on cellular samples left in contact with growing medium enriched with 13.6 mM 19F-BPA corresponding to a 11B concentration of 120 ppm: neutron autoradiography, which quantifies boron; liquid chromatography hyphenated to tandem mass spectrometry and UV-Diode Array Detection (UV-DAD), which quantifies 19F-BPA molecule; and 19F NMR spectroscopy, which detects fluorine nuclei. RESULTS: Our studies suggested that 19F-BPA is internalized by PANC-1 cells. The three methods provided consistent results of about 50% internalization fraction at 120 ppm of 11B. Small variations (less than 15%) in internalization fraction are mainly dependent on the proliferation state of the cells. CONCLUSIONS: The ability of 19F NMR spectroscopy to study 19F-BPA internalization was validated by well-established independent techniques. The multimodal approach we used suggests 19F-BPA as a promising BNCT/PBFT carrier for the treatment of pancreatic cancer. Since the quantification is performed at doses useful for BNCT/PBFT, 19F NMR can be envisaged to monitor 19F-BPA bio-distribution during the therapy.

MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters.

The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190 Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6 hours from the administration of the Gd/B/L-LDL particles (0.1 and 1 mmol kg(-1) of Gd and (10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20 days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.

Boron Neutron Capture Therapy: From Nuclear Physics to Biomedicine.

Boron Neutron Capture Therapy (BNCT) is a binary radiation treatment exploiting a nuclear reaction occurring in tumor cells [...].

Effect of spatial distribution of boron and oxygen concentration on DNA damage induced from boron neutron capture therapy using Monte Carlo simulations.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Biocompatible Iron-Boron Nanoparticles Designed for Neutron Capture Therapy Guided by Magnetic Resonance Imaging.

The combination of multiple functions in a single nanoparticle (NP) represents a key advantage of nanomedicine compared to traditional medical approaches. This is well represented by radiotherapy in which the dose of ionizing radiation should be calibrated on sensitizers biodistribution. Ideally, this is possible when the drug acts both as radiation enhancer and imaging contrast agent. Here, an easy, one-step, laser-assisted synthetic procedure is used to generate iron-boron (Fe-B) NPs featuring the set of functions required to assist neutron capture therapy (NCT) with magnetic resonance imaging. The Fe-B NPs exceed by three orders of magnitude the payload of boron isotopes contained in clinical sensitizers. The Fe-B NPs have magnetic properties of interest also for magnetophoretic accumulation in tissues and magnetic hyperthermia to assist drug permeation in tissues. Besides, Fe-B NPs are biocompatible and undergo slow degradation in the lysosomal environment that facilitates in vivo clearance through the liver-spleen-kidneys pathway. Overall, the Fe-B NPs represent a new promising tool for future exploitation in magnetic resonance imaging-guided boron NCT at higher levels of efficacy and tolerability.

Detailed dosimetry calculation for in-vitro experiments and its impact on clinical BNCT.

PURPOSE: Boron Neutron Capture Therapy (BNCT) is a form of hadrontherapy based on the selective damage caused by the products of neutron capture in 10B to tumour cells. BNCT dosimetry strongly depends on the parameters of the dose calculation models derived from radiobiological experiments. This works aims at determining an adequate dosimetry for in-vitro experiments involving irradiation of monolayer-cultured cells with photons and BNCT and assessing its impact on clinical settings. M&M: Dose calculations for rat osteosarcoma UMR-106 and human metastatic melanoma Mel-J cell survival experiments were performed using MCNP, transporting uncharged particles for KERMA determinations, and secondary particles (electrons, protons, 14C, 4He and 7Li) to compute absorbed dose in cultures. Dose-survival curves were modified according to the dose correction factors determined from computational studies. New radiobiological parameters of the photon isoeffective dose models for osteosarcoma and metastatic melanoma tumours were obtained. Dosimetry implications considering cutaneous melanoma patients treated in Argentina with BNCT were assessed and discussed. RESULTS: KERMA values for the monolayer-cultured cells overestimate absorbed doses of radiation components of interest in BNCT. Detailed dose calculations for the osteosarcoma irradiation increased the relative biological effectiveness factor RBE1% of the neutron component in more than 30%. The analysis based on melanoma cases reveals that the use of survival curves based on KERMA leads to an underestimation of the tumour doses delivered to patients. CONCLUSIONS: Considering detailed dose calculation for in-vitro experiments significantly impact on the prediction of the tumor control in patients. Therefore, proposed methods are clinically relevant.

Colocalization of tracks from boron neutron capture reactions and images of isolated cells.

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.

A Novel Approach to Design and Evaluate BNCT Neutron Beams Combining Physical, Radiobiological, and Dosimetric Figures of Merit.

(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.