EFFECT OF BORON NEUTRON CAPTURE THERAPY (BNCT) ON TUMOR MICROVASCULATURE IN THE HAMSTER CHEEK POUCH ORAL CANCER MODEL

AROMADO RF; TRIVILIN VA; HEBER EM; MOLINARI B; KREIMANN EL; SCHWINT AE; ITOIZ ME

Cordoba

Congreso; Reunion Anual SAIO 2010; 2010

Introduction: Boron Neutron Capture Therapy (BNCT) has been shown to induce tumor remission in carcinomas of the hamster cheek pouch. The mechanisms of tumor remission have not been fully elucidated. Aim: Based on prior histological observations related to vascular damage post-treatment, the aim of the present study was to assess the effects of BNCT on tumor microvasculature. Material and methods: Syrian Golden hamsters were submitted to a standard cancerization protocol in the cheek pouch (Shklar G, 1979) until the development of tumors. The animals were divided into 3 groups, i.e. (1) Hamsters with tumor not treated with BNCT (control), (2) Hamsters with tumor treated with BNCT mediated by the boron compound BPA and (3) Hamsters with tumor treated with BNCT mediated by the boron compound GB-10. Animals in groups 2 and 3 were irradiated with the thermalized epithermal neutron beam of the RA-6 Nuclear Reactor (Bariloche, Argentina) after the administration of the boron compounds, and killed humanely 1, 7 and 30 days post-irradiation. The pouches were excised, fixed and processed for labeling of blood vessel walls by immunohistochemical demonstration of Factor VIII. The end-points evaluated were: number of vascular sections, blood vessel perimeter and shape by image analysis of premalignant tissue and tumor stroma. Results: BPA-BNCT and GB-10 BNCT induced a reduction in vascular density in premalignant tissue (from 182.63±104.8 pre-treatment to 78,09±53,43 one day post BPA-BNCT and 73.95±43.26 thirty days post GB-10-BNCT). In addition, a reduction in the perimeter of tumor blood vessels and “normalization” of shape was observed post- BPA-BNCT and GB-10 BNCT (aspect ratio of 0.68±0.23 pre-treatment vs 0,77±0,17 one day post BPA-BNCT and 0.76±0.20 thirty days post-GB-10-BNCT, where 1 is the value that corresponds to the perfect circle). Conclusion: The reduction in tumor parenchyma and proliferative activity post-BNCT previously demonstrated in this model would induce a fall in vascular compression allowing for partial normalization of the structure of the vascular network.