Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model

Yoshiya Iguchi, Hiroyuki Michiue, Mizuki Kitamatsu, Yuri Hayashi, Fumiaki Takenaka, Tei ichi Nishiki, Hideki Matsui

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH]2-2Na+, BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake invitro and invivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells invitro and invivo. Furthermore, to monitor the pharmacokinetic properties of these agents invivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with 64Cu. We administered BSH-DOTA-64Cu and BSH-3R-DOTA-64Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging.

Original languageEnglish
Pages (from-to)10-17
Number of pages8
JournalBiomaterials
Volume56
DOIs
Publication statusPublished - Jul 1 2015

Keywords

  • BSH poly-arginine
  • Boron neutron capture therapy (BNCT)
  • Brain tumor
  • CPP
  • DOTA
  • Glioma
  • PET
  • TAT

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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