Gadolinium in human glioblastoma cells for gadolinium neutron capture therapy

Cancer Res. 2001 May 15;61(10):4272-7.

Abstract

157Gd is a potential agent for neutron capture cancer therapy (GdNCT). We directly observed the microdistribution of Gd in cultured human glioblastoma cells exposed to Gd-diethylenetriaminepentaacetic acid (Gd-DTPA). We demonstrated, with three independent techniques, that Gd-DTPA penetrates the plasma membrane, and we observed no deleterious effect on cell survival. A systematic microchemical analysis revealed a higher Gd accumulation in cell nuclei compared with cytoplasm. This is significant for prospective GdNCT because the proximity of Gd to DNA increases the cell-killing potential of the short-range, high-energy electrons emitted during the neutron capture reaction. We also exposed Gd-containing cells to thermal neutrons and demonstrated the GdNC reaction effectiveness in inducing cell death. These results in vitro stimulated in vivo Gd-DTPA uptake studies, currently underway, in human glioblastoma patients.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Death / radiation effects
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Gadolinium / pharmacokinetics*
  • Gadolinium / therapeutic use*
  • Gadolinium DTPA / pharmacokinetics
  • Gadolinium DTPA / toxicity
  • Glioblastoma / metabolism*
  • Glioblastoma / radiotherapy*
  • Humans
  • Isotopes
  • Mass Spectrometry
  • Neutron Capture Therapy*
  • Spectrometry, X-Ray Emission
  • Tumor Cells, Cultured

Substances

  • Isotopes
  • Gadolinium
  • Gadolinium DTPA