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[Cancer Research 61, 4272-4277, May 15, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

Gadolinium in Human Glioblastoma Cells for Gadolinium Neutron Capture Therapy1

Gelsomina De Stasio2, Patrizia Casalbore, Roberto Pallini, Benjamin Gilbert, Francesca Sanità, Maria Teresa Ciotti, Giancarlo Rosi, Armando Festinesi, Luigi Maria Larocca, Alessandro Rinelli, Didier Perret, David W. Mogk, Paolo Perfetti, Minesh P. Mehta and Delio Mercanti

Department of Physics, University of Wisconsin-Madison, and Synchrotron Radiation Center, Stoughton, Wisconsin 53589 [G. D. S., B. G.]; Istituto di Biologia Cellulare del Consiglio Nazonale delle Ricerche, I-00137 Rome, Italy [P. C.]; Istituto di Neurochirurgia, Università Cattolica del Sacro Cuore, I-00168 Rome, Italy [R. P.]; Istituto di Neurobiologia del Consiglio Nazonale delle Ricerche, 00137 Rome, Italy [F. S., M. T. C., D. M.]; Radiobiology Department, ENEA Centro Ricerche Casaccia, I-00060 Rome, Italy [G. R., A. F.]; Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, I-00168 Rome, Italy [L. M. L., A. R.]; Institut de Chimie Minérale et Analytique, Université de Lausanne, CH-1015 Lausanne, Switzerland [D. P.]; Department of Earth Sciences, Montana State University, Bozeman, Montana 59717 [D. W. M.]; Istituto di Struttura della Materia del Consiglio Nazonale delle Ricerche, I-00133 Rome, Italy [P. P.]; and Department of Human Oncology, University of Wisconsin, Madison Wisconsin 53792 [M. P. M.]

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.




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Copyright © 2001 by the American Association for Cancer Research.