Constituyentes Atomic Center

San Martín, Argentina

Constituyentes Atomic Center

San Martín, Argentina
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Hopewell J.W.,University of Oxford | Morris G.M.,Brookhaven National Laboratory | Schwint A.,Constituyentes Atomic Center | Coderre J.A.,ORA Inc
Applied Radiation and Isotopes | Year: 2011

The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint. Thus the energy spectrum of a beam will influence the RBE of this dose component. Protons from the neutron capture reaction in nitrogen have not been studied but in practice protons from nitrogen capture have been combined with the recoil proton contribution into a total proton dose. The relative biological effectiveness of the products of the neutron capture reaction in boron is derived from two factors, the RBE of the short range particles and the bio-distribution of boron, referred to collectively as the compound biological effectiveness factor. Caution is needed in the application of these factors for different normal tissues and tumors. © 2011 Elsevier Ltd.


Boggio E.F.,Bariloche Atomic Center | Longhino J.,Bariloche Atomic Center | Provenzano L.,CONICET | Farias R.,CONICET | And 5 more authors.
IFMBE Proceedings | Year: 2015

BNCT is a cancerous cells selective, nonconventional radiotherapy modality to treat malignant tumors such as glioblastoma, melanoma and recurrent head and neck cancer. It consists of a two-step procedure: first, the patient is injected with a tumor localizing drug containing a nonradioactive isotope (Boron-10) with high slow neutron capture cross-section. Secondly, the patient is irradiated with neutrons, which are absorbed by the Boron-10 agent with the subsequently nuclear reaction B-10(n,a)Li-7, thereby resulting in dose at cellular level due to the high-LET particles. The Argentine clinical facility for superficial tumors treatment is located at the RA-6 Research Reactor (Bariloche Atomic Center). Due to the beam penetration, the total absorbed dose in the first few millimeters of tissue is lower than in the maximum flux. Thus, the introduction of a suitable device over the irradiated area is considered to allow a local dose increase by means of high energy Beta particles emission, without substantially perturbing the primary in-depth dose profile. These devices are called Beta Enhancers (BE) and were studied by Monte Carlo transport code modeling, experimental measurements and retrospective treatment planning evaluation of selected nodular melanoma treatments of the Argentine BNCT patients. Pre-clinical studies were carried out in a nude mice cancer model for BNCT at the RA-6 facility, in order to preliminarily assess toxicity and efficacy of BE in-vivo implementation. Nude mice were separated into five groups of 5-9 animals each: control group, NCT (without boron agent) irradiation, NCT+BE irradiation, BNCT irradiation and BNCT+BE irradiation. The results demonstrate the technique efficacy, highlighted between NCT and NCT+BE groups. There was no toxicity evidence. © Springer International Publishing Switzerland 2015.


Fava J.,Constituyentes Atomic Center | Fava J.,National University of Costa Rica | Muller S.,Constituyentes Atomic Center | Lanzani L.,Constituyentes Atomic Center | And 3 more authors.
Studies in Applied Electromagnetics and Mechanics | Year: 2014

The electrical conductivities of ad-hoc specimens of Zircaloy-4 (Zry-4) with hydrogen contents between 5.9 and 2019 wt ppm were measured by eddy current (EC) and by van der Pauw's method. The EC evaluation was made by a non-conventional, non-comparative procedure, which gives the conductivity values through fittings of the theoretical and measured probe impedances for each specimen. Specially designed planar bobbin coil was used. The electromagnetic EC problem was solved in the test conditions. The EC conductivity measurements were made on both major faces of the specimens, i.e. the one with the oxide layer and the ground-off oxide-free face. The van der Pauw's measurements were made on the oxide-free face only. The measured electrical conductivities can be grouped in three bands corresponding to low, medium and high hydrogen contents. In all cases, the total range of conductivity variation for the studied specimens was about 2.5% of the largest value. The conductivity resolution of the procedure was about 0.8%. © 2014 The authors and IOS Press.


Molinari A.J.,Constituyentes Atomic Center | Pozzi E.C.C.,Constituyentes Atomic Center | Pozzi E.C.C.,Research and Production Reactors | Hughes A.M.,Constituyentes Atomic Center | And 13 more authors.
Radiation Research | Year: 2011

In the present study the therapeutic effect and potential toxicity of the novel "“Sequential"†boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential"BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential"BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ±2% and 91 ±3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ±5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ±12% and 60 ±22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential"BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society. All rights of reproduction in any form reserved.


Perona M.,Constituyentes Atomic Center | Perona M.,CONICET | Dagrosa A.,Constituyentes Atomic Center | Dagrosa A.,CONICET | And 8 more authors.
International Journal of Low Radiation | Year: 2010

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. Copyright © 2010 Inderscience Enterprises Ltd.


Molinari A.J.,Constituyentes Atomic Center | Pozzi E.C.C.,Constituyentes Atomic Center | Pozzi E.C.C.,Ezeiza Atomic Center | Hughes A.M.,Constituyentes Atomic Center | And 10 more authors.
Radiation Research | Year: 2012

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg 10B/kg in thalidomide-treated (Th+) and untreated (Th) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th BO). Groups I and II were given the same dose of BPA (15.5 mg 10B/kg), and all groups (IIV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 34 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity. © 2012 by Radiation Research Society.


PubMed | Constituyentes Atomic Center
Type: Journal Article | Journal: Radiation research | Year: 2011

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 3% compared to 67 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 5% in Group III (Th+ BO) and 18 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 7% in Group V (Th+ hdBO) and 47 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.


PubMed | Constituyentes Atomic Center
Type: Journal Article | Journal: Radiation research | Year: 2011

In the present study the therapeutic effect and potential toxicity of the novel Sequential boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with Sequential BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the Sequential BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 2% and 91 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 12% and 60 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. Sequential BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue.

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