Treatment of undifferentiated thyroid cancer (UTC) by boron neutron capture therapy (BNCT) using two boron compounds.

DAGROSA, MA; THOMASZ, L; LONGHINO, J; PERONA, M; CALZETTA, O; BLAUMANN, H; CABRINI, R; KAHL, S; JUVENAL, GJ; PISAREV, MA

Buenos Aires

Congreso; 13 th International Thyroid Congress; 2005

BNCT combines the selective uptake of certain boron (10B) compounds with the  irradiation of the tumor with a neutron beam. The 10B is converted into 11B, which releases an alpha particle and a nuclei of 7Li, with a high linear energy transfer (LET), killing the cells located within a 10 nm radium.  This therapy is applied to melanomas and glioblastoma multiforme. UTC does not respond to standards therapies. Previous studies have shown that a human UTC cell line (ARO) has a selective uptake of p-borophenylalanine (BPA) and that mice transplanted with  ARO cells have a 50% cure rate when treated by BNCT. When BPA is combined with a boronated porphyrin (BOPP) the amount of boron in the tumor increases. The aim of this study was to explore the response to BNCT when the two boron compounds are administered, and the effect of nicotinamide as a radiosensitizer. Materials and Methods:Nude mice were transplanted with the ARO cells and 14-20 days after were distributed into the following groups: 1) untreated controls; 2) NCT: treated with the neutron beam; 3) injected with nicotinamide (NA) (100 mg/kg body weight) during 3 days and irradiated; 4) BPA 350 mg/kg bw + irradiation; 5) BPA +NA+irradiation; 6) BPA+BOPP (60 mg/kg bw 5 days prior)+irradiation. The mice were irradiated with the neutron beam 83,4 min , corresponding to a fluence of 1.6 x 1012 n/cm2. In previous studies no effect of NA alone on tumor growth was observed. Tumor volume was measured during one month after irradiation. Catalase, aquous and lipid peroxides were determined in the tumor of some animals sacrificed at 3 and 24 hr after irradiation. Results:Control mice showed continous growth of the tumor, while NA and NCT had a partial delay. BPA, BPA+NA and BPA+BOPP showed a complete stop of growth in 100% animals. When initial tumor volume was <50 mm3 complete regression was observed in 1/4 mice from group BPA; 2/2 from BPA+NA and 7/7 from group BPA+BOPP. After 24 hr NA increased aqueous and lipidic peroxides. Conclusions:NA, via free radical generation potentiates the therapeutic effect, and simultaneous use of the two boron compounds improve efficacy, opening a new possibility for the treatment of UTC.