Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer
Nahuel Olaiz,
Andrea Monti Hughes,
Emiliano C. C. Pozzi,
Silvia Thorp,
Paula Curotto,
Verónica A. Trivillin,
Paula S. Ramos,
Mónica A. Palmieri,
Guillermo Marshall,
Amanda E. Schwint,
Marcela A. Garabalino
Affiliations
Nahuel Olaiz
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Pabellón I, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina
Andrea Monti Hughes
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2270, Buenos Aires C1425FQD, Argentina
Emiliano C. C. Pozzi
Departamento de Reactores de Investigación y Producción, Comisión Nacional de Energía Atómica (CNEA), Centro Atómico Ezeiza (CAE), Camino Real Presbítero González y Aragón 15, Buenos Aires B1802AYA, Argentina
Silvia Thorp
Sub-Gerencia Instrumentación y Control, Comisión Nacional de Energía Atómica (CNEA), Centro Atómico Ezeiza (CAE), Camino Real Presbítero González y Aragón 15, Buenos Aires B1802AYA, Argentina
Paula Curotto
Departamento de Reactores de Investigación y Producción, Comisión Nacional de Energía Atómica (CNEA), Centro Atómico Ezeiza (CAE), Camino Real Presbítero González y Aragón 15, Buenos Aires B1802AYA, Argentina
Verónica A. Trivillin
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2270, Buenos Aires C1425FQD, Argentina
Paula S. Ramos
Departamento Radiobiología, Comisión Nacional de Energía Atómica (CNEA), Centro Atómico Constituyentes (CAC), Av. General Paz 1499, San Martín, Buenos Aires B1650KNA, Argentina
Mónica A. Palmieri
Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Pabellón II, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina
Guillermo Marshall
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Pabellón I, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina
Amanda E. Schwint
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2270, Buenos Aires C1425FQD, Argentina
Marcela A. Garabalino
Departamento Radiobiología, Comisión Nacional de Energía Atómica (CNEA), Centro Atómico Constituyentes (CAC), Av. General Paz 1499, San Martín, Buenos Aires B1650KNA, Argentina
Boron neutron capture therapy (BNCT) combines preferential tumor uptake of 10B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) as the boron carrier in a hamster cheek pouch oral cancer model. The aim of the present study was to evaluate if EP could improve tumor control without enhancing the radiotoxicity of BNCT in vivo mediated by GB-10 with EP 10 min after GB-10 administration. Following cancerization, tumor-bearing hamster cheek pouches were treated with GB-10/BNCT or GB-10/BNCT + EP. Irradiations were carried out at the RA-3 Reactor. The tumor response and degree of mucositis in precancerous tissue surrounding tumors were evaluated for one month post-BNCT. The overall tumor response (partial remission (PR) + complete remission (CR)) increased significantly for protocol GB-10/BNCT + EP (92%) vs. GB-10/BNCT (48%). A statistically significant increase in the CR was observed for protocol GB-10/BNCT + EP (46%) vs. GB-10/BNCT (6%). For both protocols, the radiotoxicity (mucositis) was reversible and slight/moderate. Based on these results, we concluded that electroporation improved the therapeutic efficacy of GB-10/BNCT in vivo in the hamster cheek pouch oral cancer model without increasing the radiotoxicity.
