Therapeutic Efficacy, Radiotoxicity and Abscopal Effect of BNCT at the RA-3 Nuclear Reactor Employing Oligo-Fucoidan and Glutamine as Adjuvants in an Ectopic Colon Cancer Model in Rats.

Boron neutron capture therapy (BNCT) is based on the preferential uptake of 10B compounds by tumors, followed by neutron irradiation. The aim of this study was to assess, in an ectopic colon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immune response associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (Comb-BNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared to the "standard" BPA-BNCT protocol usually employed in clinical trials. All treatments were carried out at the RA-3 nuclear reactor. Boron biodistribution studies showed therapeutic values above 20 ppm 10B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM (p < 0.05). The parameter "incidence of tumors that underwent a reduction to ≤50% of initial tumor volume" exhibited values of 62% for Comb-BNCT alone, 82% for Comb-BNCT+GLN, 73% for Comb-BNCT+O-Fuco and only 30% for BPA-BNCT. For BPA-BNCT, the incidence of severe dermatitis was 100%, whereas it was significantly below 70% (p ≤ 0.05) for Comb-BNCT, Comb-BNCT+O-Fuco and Comb-BNCT+GLN. Considering tumors outside the treatment area, 77% of Comb-BNCT animals had a tumor volume lower than 50 mm3 vs. 30% for SHAM (p ≤ 0.005), suggesting an abscopal effect of Comb-BNCT. Inhibition of metastatic spread to lymph nodes was observed in all Comb-BNCT groups. Considering systemic aspects, CD8+ was elevated for Comb-BNCT+GLN vs. SHAM (p ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM (p ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.

The Scientific Contribution of the Kaniadakis Entropy to Nuclear Reactor Physics: A Brief Review.

In nuclear reactors, tracking the loss and production of neutrons is crucial for the safe operation of such devices. In this regard, the microscopic cross section with the Doppler broadening function is a way to represent the thermal agitation movement in a reactor core. This function usually considers the Maxwell-Boltzmann statistics for the velocity distribution. However, this distribution cannot be applied on every occasion, i.e., in conditions outside the thermal equilibrium. In order to overcome this potential limitation, Kaniadakis entropy has been used over the last seven years to generate generalised nuclear data. This short review article summarises what has been conducted so far and what has to be conducted yet.

Experimental determination of k0 and Q0 values for 121Sb, 123Sb and 130Ba targets applying covariance analysis.

This work consists of an experimental determination of k0 and Q0 for 121Sb, 123Sb and 130Ba targets. Covariance analysis has been introduced to supply not only the overall uncertainties in these parameters but also their correlations. The irradiations were performed near the core of the IEA-R1 4.5 MW swimming-pool nuclear research reactor of the Nuclear and Energy Research Institute (IPEN-CNEN/SP), in São Paulo, Brazil. The epithermal neutron flux shape parameter, alpha, at the irradiation position is very close to zero, which favors to obtain Q0 values more accurately. Two irradiations were carried out in sequence, using two sets of samples: the first with bare samples and the second inside a Cd cover. The activity measurements were carried out in a previously calibrated HPGe gamma-ray spectrometer. The measurements were corrected for: saturation, decay time, cascade summing, geometry, self-attenuation, measuring time and mass. Standard sources of 152Eu, 133Ba, 60Co and 137Cs traceable to a 4πß-γ primary system were used to obtain the HPGe gamma-ray peak efficiency as a function of the energy. The experimental efficiency curve was performed by a fourth-degree polynomial fit, in the energy range of the standard sources, 121-1408 keV, it contains all correlations between points. For energies above 1408 keV, the efficiencies were obtained by the Monte Carlo Method. The covariance matrix methodology was applied to all uncertainties involved. The final values for k0 and Q0 were compared with the literature.

Determination of k0 and Q0 for 74Se, 113In, 186W and 191Ir targets applying covariance analysis.

In the present work, the determinations of k0 and Q0 for 74Se, 113In, 186W and 191Ir targets were performed. The irradiations were conducted near the core of the IEA-R1 4.5 MW swimming-pool nuclear research reactor of the Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP - Nuclear and Energy Research Institute), in São Paulo, Brazil. The irradiation position was chosen where the neutron spectrum shape parameter α is very close to zero. For this reason, the correction to be applied for the determination of Q0 is very close to one, thus improving the accuracy of the results. For each experiment, two irradiations were carried out in sequence: the first one with bare samples and the second with a cadmium cover around the samples. All partial uncertainties were considered, applying the covariance matrix methodology. The final results were compared with the literature.

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 106 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 106 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm3. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm3. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: radiobiological studies at RA-1 Nuclear Reactor in a model of antigen-induced arthritis in rabbits.

Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.