Gadolinium in human glioblastoma cells for gadolinium neutron capture therapy.
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.
De Stasio
G
G
Department of Physics and Synchrotron Radiation Center, University of Wisconsin-Madison, Stoughton, WI 53589, USA. gdestasi@facstaff.wisc.edu
Casalbore
P
P
Pallini
R
R
Gilbert
B
B
Sanità
F
F
Ciotti
M T
MT
Rosi
G
G
Festinesi
A
A
Larocca
L M
LM
Rinelli
A
A
Perret
D
D
Mogk
D W
DW
Perfetti
P
P
Mehta
M P
MP
Mercanti
D
D
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
D007554:Isotopes; D005682:Gadolinium; D019786:Gadolinium DTPA