Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Journal Article · Tue May 01 04:00:00 EDT 2012 · Radiation and Environmental Biophysics

OSTI ID:1044919

Nigg, David W

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

• Research Organization: Idaho National Laboratory (INL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC07-05ID14517
• OSTI ID: 1044919
• Report Number(s): INL/JOU-12-26486
• Journal Information: Radiation and Environmental Biophysics, Journal Name: Radiation and Environmental Biophysics Journal Issue: 2 Vol. 51; ISSN REBPAT; ISSN 0301-634X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AQUEOUS SOLUTIONS
BLOOD
BORON
CARCINOMAS
HAMSTERS
IRRADIATION
LIPOSOMES
LIVER
MASS SPECTROSCOPY
MEMBRANES
MICE
NEOPLASMS
NEUTRON CAPTURE THERAPY
NEUTRONS
OPTIMIZATION
PATHOLOGY
SPLEEN
THERMAL NEUTRONS
TUMOR CELLS
boron neutron capture therapy