Study of 6-propyl-2-thiouracil as a radioprotector for the thyroid gland

The objective of the paper was to study the application of 6-propyl-2-thiouracil (PTU) as a radioprotector for the thyroid gland. Rat thyroid epithelial cells (FRTL-5) and human colon cancer cells (ARO81-1) were exposed to γ-irradiation with or without 1 mM PTU. Radiation response was analysed by clonogenic survival assay. Cyclic AMP levels were measured by Radioimmunoassay (RIA). The results showed that PTU increased the Surviving Cell Fraction (SF) at 2 Gy significantly (p < 0.05) in both cell lines. PTU increased extracellular levels of cAMP in all the treatments in a dose- and time-dependent manner for FRTL-5 cells. In ARO81-1 cells, a peak was observed at 24 hours in extracellular levels incubated with 1 mM PTU (36.97 ± 6.74 fmol/μg prot vs. control: 17.53 ± 3.9 fmol/μg prot, p < 0.001). Forskolin and dibutyril cAMP mimicked the effect of PTU on SF. Thus PTU appears to be a radioprotector for thyroid cells and could exert its effect through cAMP.Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pagotto, Romina. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Casal, Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentin

Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer

The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. These carcinomas are well controlled with surgery followed by therapy with 131I; however, some patients do not respond to this treatment. BPA uptake was analyzed both in vitro and in nude mice implanted with cell lines of differentiated thyroid carcinoma. The boron intracellular concentration in the different cell lines and the biodistribution studies showed the selectivity of the BPA uptake by this kind of tumor.Fil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, S.. Comisión Nacional de Energía Atómica; ArgentinaFil: Cabrini, R.. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Reference systems for the determination of 10B through autoradiography images: Application to a melanoma experimental model

The amount of 10B in tissue samples may be determined by measuring the track density in the autoradiography image produced on a nuclear track detector. Different systems were evaluated as reference standards to be used for a quantitative evaluation of boron concentration. The obtained calibration curves were applied to evaluate the concentration of 10B in melanoma tumour of NIH nude mice after a biodistribution study. The histological features observed in the tissue sections were accurately reproduced by the autoradiography images.Fil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carpano, M.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Nievas, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Pozzi, E.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Thorp, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Cabrini, R.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Liberman, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

6 Iodo-Delta Lactone Inhibits Angiogenesis in Human HT29 Colon Adenocarcinoma xenograft.

Introduction: Several studies have shown the antiproliferative effect of iodine and 5-hydroxy-6iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that moleculariodine (I2) and IL-δ, but not iodide (I-), exerts anti-neoplastic actions in different cancers. Theunderlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of thisstudy was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29colorectal cancer xenografts.Methodology and Results: HT29 cells were injected subcutaneously into the flanks of nude miceand IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenograftsshowed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression(p<0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (p<0.05). Toassess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry wasanalyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively(p<0.05), as well as it decreased VEGF and VEGF-R2 expression (p<0.05). Additionally, ourfindings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (p<0.01).Conclusion: The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as wellas induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase wouldproduce anti-proliferative effect on endothelial cells.Fil: Oglio, Romina. Comisión Nacional de Energía Atómica; ArgentinaFil: Buschittari, Federico. Comisión Nacional de Energía Atómica; ArgentinaFil: Salvarredi, Leonardo Andres. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Michaux, Jennifer. Université Libre de Bruxelles; BélgicaFil: Rodriguez, Carla. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

Experimental studies for the personalized application of boron neutron capture therapy to the treatment of cutaneous melanoma

Background: Boron neutron capture therapy (BNCT) is a binary modality based on the nuclear reaction 10B (n, α) lithium-7 (7Li) that has been used to treat a variety of tumors, among these, cutaneous melanoma (CM). In previous boron biodistribution studies in agreement with the personalized oncology, we have demonstrated that boronophenylalanine (BPA) uptake can be correlated with the tumoral temperature and viability. The main aim of these studies was to evaluate the relationship between tumoral temperature and the response to the complete BNCT. Methods: Nude mice were implanted with human melanoma cells (Mel J) and divided into different groups (Control, NCT, BNCT I and BNCT II) and irradiated with the thermal neutron beam from RA-6 (4.96× 108/cm2/sec) during 37 and 55 minutes respectively. Tumor and body temperatures were measured by Static Infrared Imaging (SIRI), and it was performed the following up of the animals. Results: Tumor growth showed a complete growth inhibition during the first 20 days after treatment in both BNCT groups (BNCT I and BNCT II vs. Control P<0.001). Considering the analogy between the Fourier's Law of Heat Conduction and the Ohm's law of Electrical Conduction, the quantity (T_tum-T_ inf)/(T_body-T_tum) was analyzed as a function of Vf/Vi (Final volume/Initial volume) ratio. A tendency to higher values of the temperature's ratios, was observed with respect to the degree of tumor control (BNCT I with a R2 of 0.3527, BNCTII with a R2 of 0.3327) in agreement with previous boron biodistribution studies. The histology and immunohistochemical studies showed larger areas of necrosis and picnotic regions and a significant decrease of the Ki-67 antibody labeling in the BNCT II group evidencing important tumor damage. Conclusions: tumoral characteristics, especially the temperature, could be used to plan a personalized treatment for each patient. As values of correlation between temperature and tumoral response showed to be weak, we considered to explore a new model of three dimension for heat transport process.Fil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Rodriguez, Carla. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María Silvina. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Boggio, Esteban Fabián. Comisión Nacional de Energía Atómica; ArgentinaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Experimental studies of boronophenylalanine (10BPA) biodistribution for the individually tailored application of boron neutron capture therapy (BNCT) for malignant melanoma treatment

Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina (10BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 106 MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 2.6 mg/g in tumor, with individual values ranging between 11.7 and 52.0 mg/g of 10B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37C and 23C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R2 Z 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R2 Z 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.Fil: Carpano, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, Carla Beatriz. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Brandizzi, Daniel. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Cabrini, Romulo Luis. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Qualitative autoradiography with polycarbonate foils enables histological and track analyses on the same section

Neutron autoradiography is an imaging methodology that enables analysis of the spatial distribution of heavy ion emitters in a given material. In particular, it allows localization of 10 B in a tissue section put in contact with a nuclear track detector. Boron imaging is essential when considering boron neutron capture therapy as an option for treating cancerous tumors. A description of the autoradiography method is presented together with specific characteristics and technical details developed in our laboratory. We propose a new mounting technique to compare autoradiography images with the same section that gave rise to the latent tracks. The solid state nuclear track detector is polycarbonate, because it can be processed rapidly to obtain the autoradiographic results. It is a transparent material, which allows visualization of the sections mounted on it. Tissue can be removed easily and background is minimal.Fil: Portu, Agustina Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Cabrini, Rómulo L.. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica; Argentin

Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy

© 2020 by the authors.One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro–BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy.This research was funded by FCE-ANII (FCE_3_2018_1_148288), Institut Pasteur de Montevideo— FOCEM. M.C., M.F.G., E.T., and H.C. are Sistema Nacional de Investigadores- Agencia Nacional de Investigación e Innovación (ANII) researchers. M.C. thanks CSIC-Universidad de la República (UdelaR) (Grupo I + D, CSIC-421) for his scholarships. M.C. thanks funding from ANII for his doctoral-scholarship (POS_NAC_2015_1_110068). C.V. and F.T. thanks MINECO (CTQ2016-75150-R) for financial support.Peer reviewe

Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells

We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p<0.05) and diminished radiation- induced apoptosis. In addition, we observed that the level of antioxidant enzymes’ activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p<0.01) and dibutyryl cAMP (p<0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Casal, Mariana. Comisión Nacional de Energía Atómica; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

In vitro studies of DNA damage and repair mechanisms induced by BNCT in a poorly differentiated thyroid carcinoma cell line

Boron neutron capture therapy (BNCT) for aggressive tumors is based on nuclear reaction [10B (n, α) 7Li]. Previously, we demonstrated that BNCT could be applied for the treatment of undifferentiated thyroid carcinoma. The aim of the present study was to describe the DNA damage pattern and the repair pathways that are activated by BNCT in thyroid cells. We analyzed γH2AX foci and the expression of Ku70, Rad51 and Rad54, main effector enzymes of non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, respectively, in thyroid follicular carcinoma cells. The studied groups were: (1) C [no irradiation], (2) gamma [60Co source], (3) N [neutron beam alone], (4) BNCT [neutron beam plus 10 µg 10B/ml of boronphenylalanine (10BPA)]. The total absorbed dose was always 3 Gy. The results showed that the number of nuclear γH2AX foci was higher in the gamma group than in the N and BNCT groups (30 min–24 h) (p < 0.001). However, the focus size was significantly larger in BNCT compared to other groups (p < 0.01). The analysis of repair enzymes showed a significant increase in Rad51 and Rad54 mRNA at 4 and 6 h, respectively; in both N and BNCT groups and the expression of Ku70 did not show significant differences between groups. These findings are consistent with an activation of HRR mechanism in thyroid cells. A melanoma cell line showed different DNA damage pattern and activation of both repair pathways. These results will allow us to evaluate different blocking points, to potentiate the damage induced by BNCT.Fil: Rodriguez, C.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Carpano, M.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Curotto, P.. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; ArgentinaFil: Thorp, S.. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; ArgentinaFil: Casal, M.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentin