Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels

Abstract Background. We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalizat...

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Published in:Acta oncologica 2015-01, Vol.54 (1), p.99-106
Main Authors: Molinari, Ana J., Thorp, Silvia I., Portu, Agustina M., Saint Martin, Gisela, Pozzi, Emiliano C. C., Heber, Elisa M., Bortolussi, Silva, Itoiz, Maria E., Aromando, Romina F., Monti Hughes, Andrea, Garabalino, Marcela A., Altieri, Saverio, Trivillin, Verónica A., Schwint, Amanda E.
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene
Angiogenesis Inhibitors - therapeutic use
Animals
Boron Compounds - pharmacokinetics
Boron Compounds - therapeutic use
Boron Neutron Capture Therapy - methods
Carcinogens
Cricetinae
Mesocricetus
Mouth Neoplasms - blood supply
Mouth Neoplasms - chemically induced
Mouth Neoplasms - metabolism
Mouth Neoplasms - radiotherapy
Neovascularization, Pathologic - drug therapy
Phenylalanine - analogs & derivatives
Phenylalanine - pharmacokinetics
Phenylalanine - therapeutic use
Precancerous Conditions - blood supply
Precancerous Conditions - chemically induced
Precancerous Conditions - metabolism
Precancerous Conditions - radiotherapy
Thalidomide - therapeutic use
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Summary:Abstract Background. We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Material and Methods. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Results. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Conclusion. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.
ISSN:0284-186X
1651-226X
DOI:10.3109/0284186X.2014.925140