Studies for the application of boron neutron capture therapy (BNCT) to the treatment of differentiated thyroid cancer (DTC)

DAGROSA, MA; THOMASZ, L; CARPANO, M; PERONA, M; NIEVAS, S; THORP, S; POZZI, E; JUVENAL, G; PISAREV , M

Buenos Aires

Congreso; 14th International Congress on Neutron Capture Therapy; 2010

CNEA, UNSAM, ROFFO

More than 80% of patients with thyroid neoplasms present differentiated carcinoma (DTC). These carcinomas are treated by surgery followed by therapy with 131I and mostly these forms are well controlled. However in some patients recurrence of the tumor is observed. In previous studies we have shown that BNCT can be a possibility for the treatment of undifferentiated thyroid cancer (UTC) and could be an alternative for the patients with DTC. The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. Materials and Methods: The human cell lines of follicular (WRO) and papillar carcinomas (TPC-1) were grown in RPMI and modified DMEM medium respectively. Both supplemented with 10% of SFB. The cell line of rat normal thyroid, FRTL-5, used as normal control, was cultured in DMEM/F12. The uptakes of 125I and p-borophenylalanine BPA (6.93mM) were studied. The intracellular boron concentration was measured by ICP-OES at 2 hr post incubation. The NIH strain of male nude mice, aged 6 to 8 weeks and weighing 20 to 25 g were implanted (s.c) in the back right flank with different concentrations of tumor cells. The size of the tumors was measured with a caliper twice or three times a week. To evaluate the BPA uptake, animals were injected with the boron compound at a dose of 350 mg/Kg b.w (ip) and sacrificed at 0.5; 1; 1.5 and 2.0 hr post administration. Boron measurements in tissues and blood were performed. Results and Discussion: The radioactive 125I uptake was significative lower for the tumor cells than for the normal cells (p<0.01). The ratios between FRTL-5 and WRO and TPC-1 respectively were 305 and 76. On the contrary the boron intracellular concentration ratios between WRO and TPC-1 Vs FRTL-5 were 5.44 and 2.97, showing the selectivity of the BPA uptake by the tumor cells. The animals implanted with 1.5 x106 cells showed that the tumors started to grow after 25 days post implantation. The BPA uptake showed a peak of around 17 ppm at 1 hr post injection. The ratios between tumor and normal surrounding tissues (blood and distal skin) were 2.6 and 2. The studied cell lines showed a biological behavior similar to that of differentiated thyroid carcinoma in patients. The uptake of BPA in CDT cells is lower than that observed in undifferentiated thyroid cells but selective for the tumor and BNCT can be an alternative for the treatment of this pathology.