Comparison of three treatment regimens of sodium butyrate as a chemotherapeutic agent on boronophenylalanine (BPA) uptake previous neutron irradiation in pre clinical studies of boron neutron capture therapy (BNCT) for thyroid carcinoma.

PERONA, M; CARPANO, M; RODRIGUEZ , C; NIEVAS, S; OLIVERA, M; PISAREV M; JUVENAL , G; DAGROSA, MA

Tsukuba

Congreso; 15TH International Congress on Neutron Capture Therapy; 2012

Background: We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC). However new strategies are being assayed in order to optimize its application. Histone deacetylase inhibitors (HDAC-I) like sodium butyrate (NaB), are emerging as a new class of chemotherapeutic agents which target the epigenome. Since histone hyperacetylation mediates changes in chromatin conformation, HDAC-I are involved in different epigenetically controlled activities like apoptosis, proliferation, cell differentiation, induction of cell cycle arrest and motility. The purpose of the present studies was to analyze different treatment regimens of combination of NaB and boronophenylalanine (BPA) uptake in animals bearing transplants of a human thyroid carcinoma Methods: NIH nude mice of 6-8 weeks were implanted (s.c.) with 106 of human follicular thyroid carcinoma cells (WRO). Three regimens were evaluated in 48 animals after 15 days when tumors had a size between 50 and 100 mm3. Group 1 (n=10): BPA and NaB (50 mM) via i.p. at a dose of 110 mg/kg b.w. 24 h before boron compound administration; group 2 (n=10): BPA and NaB 3.4% in the water ad libitum during a month after 15 days post-implantation; group 3 (n=10): BPA alone. In all the groups BPA was injected at a dose of 350 mg/Kg b.w. (i.p.) and the animals were sacrificed at 2 h post-administration. Boron measurements in tissues and blood were performed by ICP-OES. A control group without NaB (n=6) for each regimen was included. The tumor growth and the body weight were determined twice a week during a month. Results: The administration of NaB 3.4% during a month previous to BNCT did not modify the body weight of the mice and decreased the tumor growth compared to its control group (p