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

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Abstract

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.

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Acknowledgments

This study was supported in part by the University of Missouri through the MU International Institute for Nano and Molecular Medicine, the United States Department of Energy through the Idaho National Laboratory Faculty-Staff Exchange and Division Initiative Support programs, and a grant from the National Agency for the Promotion of Science and Technology of Argentina (PICT 2006—00700). The authors wish to acknowledge the expert advice and generous support of Dr. Claudio Devida and his team with ICP-MS boron measurements.

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Authors and Affiliations

  1. Department of Radiobiology, National Atomic Energy Commission, Avenida General Paz 1499, B1650KNA, San Martin, Buenos Aires, Argentina

    Elisa M. Heber, Marcela A. Garabalino, Ana J. Molinari, Andrea Monti Hughes, Verónica A. Trivillin & Amanda E. Schwint

  2. International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO, USA

    Peter J. Kueffer, Mark W. Lee Jr. & M. Frederick Hawthorne

  3. Department of Research and Production Reactors, National Atomic Energy Commission, Presbítero Juan González y Aragon 15, B1802AYA, Ezeiza, Buenos Aires, Argentina

    Emiliano C. C. Pozzi

  4. Idaho National Laboratory, 2525 North Fremont Street, P.O. Box 1625, Idaho Falls, ID, 83415, USA

    David W. Nigg & William Bauer

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  1. Elisa M. Heber
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  2. Peter J. Kueffer
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  3. Mark W. Lee Jr.
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  4. M. Frederick Hawthorne
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  5. Marcela A. Garabalino
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  6. Ana J. Molinari
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  7. David W. Nigg
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  8. William Bauer
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  9. Andrea Monti Hughes
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  10. Emiliano C. C. Pozzi
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  11. Verónica A. Trivillin
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  12. Amanda E. Schwint
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Correspondence to Amanda E. Schwint.

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Heber, E.M., Kueffer, P.J., Lee, M.W. et al. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential. Radiat Environ Biophys 51, 195–204 (2012). https://doi.org/10.1007/s00411-011-0399-0

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