Comparative studies in the use of Beta Enhancers devices as a complementary tool to BNCT for the treatment of cancer

NIEVAS S; BOGGIO E; BROLLO F; LONGHINO J; DAGROSA MA

Granada

Congreso; 19TH INTERNATIONAL CONGRESS OF NEUTRON CAPTURE THERAPY (ICNCT); 2021

Introduction: The BNCT clinical trials in Argentina were restarted after changes in the beam in the RA-6 reactor. Due to the characteristics of the neutron beam, the maximum dose is not on the surface of the tumour, but at 1 cm depth. Some materials such as Rh, Ag and In have a high effective neutron capture section, rapid decay activation products and high energy beta particles emission. Since beta radiation has a short range of tissue penetration, these devices called Beta Enhancers (BE) can be used to compensate for the BNCT surface dose gradient or even to significantly increase it. In previous studies we showed its effectiveness in controlling tumour growth and increased cell damage and we demonstrated that three devices would be non-toxic and effective as complementary tools to BNCT for the treatment of superficial tumours. Several experimental studies of BNCT for tumours superficially implanted in the nude mice were performed and different parameters were followed up in order to evaluate the efficacy therapeutic of BNCT. Currently, the conception of cancer is that solid tumors have a complex cellular distribution within which appear cells with different proliferative capacity or different resistance to drugs. These cell populations shares characteristics that makes them unique as a niche that maintains tumour survival, they are cancer stem cells (CSCs). The CSCs are associated with multiple resistance mechanisms, including chemo and radioresistance, therefore controlling the proliferation of CSC is critical. It was proposed that CD133 could be a good marker of CSCs. Many therapies are not totally effective eliminating most of tumour cells and some tumours reappear. If the importance of the stem cells in this reappearance is demonstrated, the new therapies should be targeted specifically against CSCs in an attempt to prevent resistance to them and tumor regeneration. So far there are no data linking BNCT therapy with CSCs, so it is useful to cover this study. Objective: To evaluate the use of BE as a complementary tool in BNCT to the treatment of superficial tumors and to analyze the presence and persistence of CSCs after treatment. Materials and Methods: NIH nude mice were implanted subcutaneously with HT29 colon cancer human line cells, developing tumors at day 15. There were two irradiations: In the first irradiation the animals were divided into 4 groups: Control; NCT; NCT + BE-Rh; BNCT and BNCT + BE-Rh. In the second irradiation the animals were divided into 5 groups: Control; BNCT + BE-Rh; BNCT + BE-Ag; BNCT + BE-In. Animals of groups 2, 3, 4 and 5 received 350 mg/kg of body weight of 10BPA. The mice received subcutaneous anesthesia and were irradiated at a specific positioning for 37 minutes in first irradiation and 45.3 minutes in second irradiation with a neutron flux of 4.96x108n/cm2sec. Results: Animal monitoring after irradiation does not show any signs of radiotoxicity. Tumor growth curves were developed as a function of time, with a decrease in growth in all groups treated with the flakes, being less in groups with Rh. Histological studies had a correlation between the area of tumor necrosis and the total physical dose absorbed. A lower presence of cancer stem cells (CSC) was observed after three weeks of treatment. Conclusions: All types of BE showed efficacy in controlling tumor growth post irradiation. Rhodium BE could cause greater tumor damage, however more studies are required to clarify the radiochemical processes involved. Positive CSC populations are present in the Control group, and decrease in the first week after treatment in BNCT-BE groups and their persistence would be related to the tumor proliferation observed one month after treatment.