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

Acta Oncol. 2015 Jan;54(1):99-106. doi: 10.3109/0284186X.2014.925140. Epub 2014 Jun 24.

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.

MeSH terms

  • 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

Substances

  • Angiogenesis Inhibitors
  • Boron Compounds
  • Carcinogens
  • decahydrodecaborate
  • Phenylalanine
  • Thalidomide
  • 9,10-Dimethyl-1,2-benzanthracene