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Optimization of boron neutron capture therapy for the treatment of undifferentiated thyroid cancer.

Author	Maria Alejandra Dagrosa, Lisa Thomasz, Juan Longhino, Marina Perona, Osvaldo Calzetta, Herman Blaumann, Raúl Jiménez Rebagliati, Romulo Cabrini, Steven Kahl, Guillermo Juan Juvenal, Mario Alberto Pisarev
Citation Information	International journal of radiation oncology, biology, physics, 69:1059-66 (2007)
Keywords	Animals, Apoptosis, Boron Compounds, Boron Neutron Capture Therapy, Cell Line, Tumor, Deuteroporphyrins, Disease-Free Survival, Drug Therapy, Combination, Humans, Male, Mice, Mice, Nude, Niacinamide, Phenylalanine, Radiation-Sensitizing Agents, Radiotherapy Dosage, Remission Induction, Thyroid Neoplasms, Tissue Distribution
Related Products	S7100
Pub Med ID	17967301

PURPOSE: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis (alpha,beta-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. METHODS AND MATERIALS: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60 mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10(8) n/cm(2)/sec for 83.4 min. RESULTS: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm(3) or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. CONCLUSIONS: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.