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

Abstract

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.

• Authors: 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
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 69 Issue 4 Pg. 1059-66 (Nov 15 2007) ISSN: 0360-3016 [Print] United States
• PMID: 17967301 (Publication Type: Journal Article)

Chemical References

• 2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester
• Boron Compounds
• Deuteroporphyrins
• Radiation-Sensitizing Agents
• Niacinamide
• Phenylalanine
• 4-boronophenylalanine

Topics

• Animals
• Apoptosis
• Boron Compounds (pharmacokinetics, therapeutic use)
• Boron Neutron Capture Therapy (methods)
• Cell Line, Tumor
• Deuteroporphyrins (therapeutic use)
• Disease-Free Survival
• Drug Therapy, Combination
• Humans
• Male
• Mice
• Mice, Nude
• Niacinamide (therapeutic use)
• Phenylalanine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Radiation-Sensitizing Agents (therapeutic use)
• Radiotherapy Dosage
• Remission Induction
• Thyroid Neoplasms (metabolism, pathology, radiotherapy)
• Tissue Distribution