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Electroporation optimizes the uptake of boron-10 by tumor for boron neutron capture therapy (BNCT) mediated by GB-10: a boron biodistribution study in the hamster cheek pouch oral cancer model

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Abstract

Boron neutron capture therapy (BNCT) is a promising cancer binary therapy modality that utilizes the nuclear capture reaction of thermal neutrons by boron-10 resulting in a localized release of high- and low-linear energy transfer (LET) radiation. Electrochemotherapy (ECT) is based on electroporation (EP) that induces opening of pores in cell membranes, allowing the entry of compounds. Because EP is applied locally to a tumor, the compound is incorporated preferentially by tumor cells. Based on the knowledge that the therapeutic success of BNCT depends centrally on the boron content in tumor and normal tissues and that EP has proven to be an excellent facilitator of tumor biodistribution of an anti-tumor agent, the aim of this study was to evaluate if EP can optimize the delivery of boronated compounds. We performed biodistribution studies and qualitative microdistribution analyses of boron employing the boron compound sodium decahydrodecaborate (GB-10) + EP in the hamster cheek pouch oral cancer model. Syrian hamsters with chemically induced exophytic squamous cell carcinomas were used. A typical EP treatment was applied to each tumor, varying the moment of application with respect to the administration of GB-10 (early or late). The results of this study showed a significant increase in the absolute and relative tumor boron concentration and optimization of the qualitative microdistribution of boron by the use of early EP + GB-10 versus GB-10 without EP. This strategy could be a tool to improve the therapeutic efficacy of BNCT/GB-10 in vivo.

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Funding

This study was partially funded by Comisión Nacional de Energía Atómica and Instituto Nacional del Cáncer, Argentina.

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Author notes

  1. Marcela A. Garabalino and Nahuel Olaiz contributed equally.

Authors and Affiliations

  1. Departamento de Radiobiología, Comisión Nacional de Energía Atómica, Centro Atómico Constituyentes, Avenida General Paz 1499, B1650KNA, San Martin, Provincia Buenos Aires, Argentina

    Marcela A. Garabalino, Agustina Portu, Gisela Saint Martin, Andrea Monti Hughes, Verónica A. Trivillin & Amanda E. Schwint

  2. Departamento de Sistemas complejos, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA, Ciudad Autónoma De Buenos Aires, Argentina

    Nahuel Olaiz & Guillermo Marshall

  3. Sub-gerencia Instrumentación y Control, Centro Atómico Ezeiza, Camino Real Presbítero González y Aragón 15, B1802AYA, Ezeiza, Provincia Buenos Aires, Argentina

    Silvia I. Thorp

  4. Departamento de Reactores de Investigación y Producción, Centro Atómico Ezeiza, Camino Real Presbítero González y Aragón 15, B1802AYA, Ezeiza, Provincia Buenos Aires, Argentina

    Emiliano C. C. Pozzi & Paula Curotto

  5. Instituto de Oncología Angel H. Roffo, Avenida San Martin 5481, C1417DTB, Ciudad Autónoma De Buenos Aires, Argentina

    Lucas L. Colombo

  6. Departamento de Anatomía Patología, Facultad de Odontología, Universidad de Buenos Aires, Marcelo T. de Alvear 2142, C1122AAH, Ciudad Autónoma De Buenos Aires, Argentina

    María E. Itoiz

  7. Idaho National Laboratory, 2525 Fremont Ave, Idaho Falls, ID, 83402, USA

    David W. Nigg

  8. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, C1425FQB, Cuidad Autónoma De Buenos Aires, Argentina

    Nahuel Olaiz, Agustina Portu, Gisela Saint Martin, Emiliano C. C. Pozzi, Paula Curotto, Andrea Monti Hughes, Lucas L. Colombo, Verónica A. Trivillin, Guillermo Marshall & Amanda E. Schwint

Authors
  1. Marcela A. Garabalino
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  2. Nahuel Olaiz
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  3. Agustina Portu
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  4. Gisela Saint Martin
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  5. Silvia I. Thorp
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  6. Emiliano C. C. Pozzi
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  7. Paula Curotto
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  8. María E. Itoiz
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  9. Andrea Monti Hughes
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  10. Lucas L. Colombo
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  11. David W. Nigg
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  12. Verónica A. Trivillin
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  13. Guillermo Marshall
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  14. Amanda E. Schwint
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Corresponding author

Correspondence to Marcela A. Garabalino.

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Garabalino, M.A., Olaiz, N., Portu, A. et al. Electroporation optimizes the uptake of boron-10 by tumor for boron neutron capture therapy (BNCT) mediated by GB-10: a boron biodistribution study in the hamster cheek pouch oral cancer model. Radiat Environ Biophys 58, 455–467 (2019). https://doi.org/10.1007/s00411-019-00796-z

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  • DOI: https://doi.org/10.1007/s00411-019-00796-z

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