Optimization of boron neutron capture therapy (BNCT) for the individual treatment of cutaneous melanoma

CARPANO, M; NIEVAS, S; SANTA CRUZ, G; OLIVERA, M; PERONA, M; RODRIGUEZ , C; CABRINI, R; BOGGIO, E; LONGHINO, J; FERNANDEZ, C; JUVENAL, GJ; PISAREV, M; DAGROSA, MA

Helsinki

Congreso; 16 th Internation Congress on Boron Neutron capture therapy (BNCT).; 2014

BNCT is a radiation therapy that provides a way to destroy tumor cells without harming surrounding normal tissue significantly. The success of this therapy depends primarily on the ability of the boron compound to concentrate selectively in the tumor. In our laboratory, in order to optimize the individual application of BNCT to the cutaneous melanoma, we performed different studies. Previously we have shown that different human melanoma cell lines have different patterns of boronophenylalanine (10BPA) uptake. On the other hand, mice implanted with one of these cell lines developed tumors with different biological and physical characteristics, and we found a positive correlation between BPA uptake, percentage of viable cells and tumor temperature. The aim of these studies was to evaluate if the observed correlation between intratumoral boron content, temperature and viability translates into a better response to neutron irradiation. Materials and Methods: 60 male NIH nude mice were implanted subcutaneously (sc) in the right flank with 3 x106 of Mel J cells. The animals were divided into 3 groups: 1) Control: without irradiation and BPA; 2) NCT: irradiated with the neutron beam; 3) BNCT: irradiated with the neutron beam plus BPA (350 mg/kg b.w). Each mouse was individualized and was transported by plane to the Bariloche Atomic Center (CAB) to be irradiated in the thermal neutron beam of RA6 (Flux: 4.96 108 n/cm2. Animals were anesthetized s.c. with diazepam and ketamine (200 mg/kg b.w) and irradiated in groups of 8 for 37.0 ± 0.5 min. Tumor growth and tumoral histology were evaluated for 40 days post treatment. Body and tumor temperatures of each mouse were measured by infrared thermography, pre and post treatment, as a no invasive indicator of boron uptake and histology. Results: Tumor continue to grow in the animals of the Control group, reaching a value of 30.81 in the relative tumoral volume at 40 days post treatment. At the same time, the NCT group reached a relative tumor volume of 28.72, while the BNCT group showed complete stop in the tumor growth during the first 20 days after treatment, but reaching an average value of relative volumen of 3.64 at the 40 day. Total physical absorbed doses were 13.4 ± 5.1 % cGy/min for BNCT group and 5.8 ± 1.8 % cGy/min for NCT group. Animals with lower differences between the body and the tumoral temperatures and higher tumor temperature had a better response to treatment. Conclusion: The temperature measurement by termography in each mouse could be used as a predictive marker of therapeutic success for optimizing individual BNCT therapy.