Experimental studies for the personalized application of boron neutron capture therapy to the treatment of cutaneous melanoma

Abstract

Background: Boron neutron capture therapy (BNCT) is a binary modality based on the nuclear reaction 10B (n, α) lithium-7 (7Li) that has been used to treat a variety of tumors, among these, cutaneous melanoma (CM). In previous boron biodistribution studies in agreement with the personalized oncology, we have demonstrated that boronophenylalanine (BPA) uptake can be correlated with the tumoral temperature and viability. The main aim of these studies was to evaluate the relationship between tumoral temperature and the response to the complete BNCT. Methods: Nude mice were implanted with human melanoma cells (Mel J) and divided into different groups (Control, NCT, BNCT I and BNCT II) and irradiated with the thermal neutron beam from RA-6 (4.96× 108/cm2/sec) during 37 and 55 minutes respectively. Tumor and body temperatures were measured by Static Infrared Imaging (SIRI), and it was performed the following up of the animals. Results: Tumor growth showed a complete growth inhibition during the first 20 days after treatment in both BNCT groups (BNCT I and BNCT II vs. Control P<0.001). Considering the analogy between the Fourier's Law of Heat Conduction and the Ohm's law of Electrical Conduction, the quantity (T_tum-T_ inf)/(T_body-T_tum) was analyzed as a function of Vf/Vi (Final volume/Initial volume) ratio. A tendency to higher values of the temperature's ratios, was observed with respect to the degree of tumor control (BNCT I with a R2 of 0.3527, BNCTII with a R2 of 0.3327) in agreement with previous boron biodistribution studies. The histology and immunohistochemical studies showed larger areas of necrosis and picnotic regions and a significant decrease of the Ki-67 antibody labeling in the BNCT II group evidencing important tumor damage. Conclusions: tumoral characteristics, especially the temperature, could be used to plan a personalized treatment for each patient. As values of correlation between temperature and tumoral response showed to be weak, we considered to explore a new model of three dimension for heat transport process.