title: Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.
abstract: Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.
authors.affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, 1500 Vital Brasil Avenue, São Paulo, SP 05503-900, Brazil. fernandafaiao@usp.br
authors.forename: Fernanda
authors.initials: F
authors.lastname: Faião-Flores
authors.forename: Paulo Rogério Pinto
authors.initials: PR
authors.lastname: Coelho
authors.forename: João Dias Toledo
authors.initials: JD
authors.lastname: Arruda-Neto
authors.forename: Maria Aparecida Pires
authors.initials: MA
authors.lastname: Camillo
authors.forename: Silvya Stuchi
authors.initials: SS
authors.lastname: Maria-Engler
authors.forename: Rose Eli Grassi
authors.initials: RE
authors.lastname: Rici
authors.forename: Jorge Eduardo Souza
authors.initials: JE
authors.lastname: Sarkis
authors.forename: Durvanei Augusto
authors.initials: DA
authors.lastname: Maria
mesh_terms: D000818:Animals; D001895:Boron / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: D008543:Melanins; D001895:Boron