Evaluación de los efectos biológicos obtenidos en la utilización de dispositivos Beta Enhancers como herramienta complementaria a la terapia por captura neutrónica en boro para el tratamiento del cáncer

NIEVAS S; LUNA M; CARPANO M,; PISAREV M; JUVENAL G; LONGHINO J,; DAGROSA MA

Buenos Aire

Jornada; Jornadas CUIA (Consorzio Interuniversitario italiano per lꞌArgentina); 2018

FICEN, Universidad Favaloro,

Introduction: BNCT clinical trials in Argentina restarted in 2015 after modifications in the nuclear reactor RA6. Due to the neutron beam characteristics the maximum dose is not on the surface of the tumour but a few centimetres deep. Some materials such as rhodium, silver and indium have a high effective neutron capture section, rapid decay activation products and high energy beta particles emission. As beta radiation has a short range of tissue penetration these devices named beta enhancers (BE) can be used to compensate or even significantly increase the surface dose gradient BNCT. In previous studies we demonstrated that nude mice, bearing surface tumours and irradiated by BNCT with the addition of rhodium BE devices showed no signs of toxicity and effectiveness to control the tumour growth. Objective: Evaluation of radiotoxicity and effectiveness of three BE devices (rhodium, silver and indium) as a complementary tool of BNCT. Materials and Methods: Sixty NIH nude mice (25-30 g body weight) were implanted subcutaneously with cells from the HT-29 colon cancer human cell line, developing tumours between 150 and 200 mm3 of size at day 15. The animals were divided into 4 groups: 1) Control; 2) BNCT + BE rhodium; 3) BNCT + BE silver; 4) BNCT + BE indium. Animals of groups 2, 3 and 4 received 350 mg/kg of body weight of borophenylalanine (10BPA). The mice received subcutaneous anesthesia and were irradiated at a specific positioning for 42.5 minutes with a neutron flux of 4.96 108 n/cm2.sec. The animal's body weight and the tumor growth were evaluated. Also histological and immunohistochemical studies were performed. Results: The animal did not show any signs of radiotoxicity (body weight during the time of evaluation). Some animals in group 4 showed mild erythema in the tumor area, which reverted after the first week. Complete inhibition of tumor growth was observed in the three BNCT-BE groups during the first three weeks. The histological studies performed at seven days showed a lower percentage of the viable area (taking in account the tumour volume) in the three treated groups, being even lower for the group 4. The analysis of cells in mitosis process showed that the number of cells was lower in the three treatments. The number of vacuoles as an indicator of death cell by autophagy showed a high value for the three BNCT groups being larger for group 4. The CD133 and CD166 positive cells indicated the presence of cancer stem cells (CSCs) in the viable area of the tumour. Its persistence, although diminished, a week after irradiation, would seem to be associated with tumour proliferation and loss of control over the growth of tumour with any of the devices used. The total physical doses absorbed by the tumours did not show significant differences between the three irradiated groups and were of 7.31 Gy for BNCT-Rh, of 7.34 Gy for BNCT-Ag and of 6.59 Gy for BNCT-In. Conclusions: These studies demonstrated that the three devices would be non-toxic and effective as complementary tools to BNCT for the treatment of superficial tumours. At the macroscopic level, no significant differences in tumour growth were observed among the three groups. However, at the microscopic level with the BE of Indium, a greater biological effect was obtained. To understand the higher cell damage observed with BE of Indium will be study the radiochemical processes involved.