title: Gadolinium in human glioblastoma cells for gadolinium neutron capture therapy.
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.
authors.affiliation: Department of Physics and Synchrotron Radiation Center, University of Wisconsin-Madison, Stoughton, WI 53589, USA. gdestasi@facstaff.wisc.edu
authors.forename: G
authors.initials: G
authors.lastname: De Stasio
authors.forename: P
authors.initials: P
authors.lastname: Casalbore
authors.forename: R
authors.initials: R
authors.lastname: Pallini
authors.forename: B
authors.initials: B
authors.lastname: Gilbert
authors.forename: F
authors.initials: F
authors.lastname: Sanità
authors.forename: M T
authors.initials: MT
authors.lastname: Ciotti
authors.forename: G
authors.initials: G
authors.lastname: Rosi
authors.forename: A
authors.initials: A
authors.lastname: Festinesi
authors.forename: L M
authors.initials: LM
authors.lastname: Larocca
authors.forename: A
authors.initials: A
authors.lastname: Rinelli
authors.forename: D
authors.initials: D
authors.lastname: Perret
authors.forename: D W
authors.initials: DW
authors.lastname: Mogk
authors.forename: P
authors.initials: P
authors.lastname: Perfetti
authors.forename: M P
authors.initials: MP
authors.lastname: Mehta
authors.forename: D
authors.initials: D
authors.lastname: Mercanti
mesh_terms: D016923:Cell Death / Q000528:radiation effects; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005682:Gadolinium / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics / Q000633:toxicity; D005909:Glioblastoma / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D007554:Isotopes; D013058:Mass Spectrometry; D017247:Neutron Capture Therapy; D013052:Spectrometry, X-Ray Emission; D014407:Tumor Cells, Cultured
chemical_list: D007554:Isotopes; D005682:Gadolinium; D019786:Gadolinium DTPA