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Motexafin-Gadolinium Taken Up In vitro by at Least 90% of Glioblastoma Cell Nuclei

Authors' Affiliations: ¹ Department of Physics and Synchrotron Radiation Center, University of Wisconsin-Madison, Stoughton, Winconsin; Departments of ² Human Oncology, ³ Statistics, and ⁴ Surgery, University of Wisconsin, Madison, Wisconsin; ⁵ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California; ⁶ Lawrence Berkeley National Laboratory, Berkeley, California; and ⁷ Institut National de la Sante et de la Recherche Medicale U647/Rayonnement Synchrotron et Recherche Médicale at European Synchrotron Radiation Facility and Unité Imagerie par Résonance Magnétique, Centre Hospitalier Universitaire, Grenoble, France

Requests for reprints: Gelsomina De Stasio, Department of Physics and Synchrotron Radiation Center, University of Wisconsin-Madison, 3731 Schneider Drive, Stoughton, WI 53589. Phone: 608-877-2000; Fax: 608-877-2001; E-mail: pupa{at}src.wisc.edu.

Purpose: We present preclinical data showing the in vitro intranuclear uptake of motexafin gadolinium by glioblastoma multiforme cells, which could serve as a prelude to the future development of radiosensitizing techniques, such as gadolinium synchrotron stereotactic radiotherapy (GdSSR), a new putative treatment for glioblastoma multiforme.

Experimental Design: In this approach, administration of a tumor-seeking Gd-containing compound would be followed by stereotactic external beam radiotherapy with 51-keV photons from a synchrotron source. At least two criteria must be satisfied before this therapy can be established: Gd must accumulate in cancer cells and spare the normal tissue; Gd must be present in almost all the cancer cell nuclei. We address the in vitro intranuclear uptake of motexafin gadolinium in this article. We analyzed the Gd distribution with subcellular resolution in four human glioblastoma cell lines, using three independent methods: two novel synchrotron spectromicroscopic techniques and one confocal microscopy. We present in vitro evidence that the majority of the cell nuclei take up motexafin gadolinium, a drug that is known to selectively reach glioblastoma multiforme.

Results: With all three methods, we found Gd in at least 90% of the cell nuclei. The results are highly reproducible across different cell lines. The present data provide evidence for further studies, with the goal of developing GdSSR, a process that will require further in vivo animal and future clinical studies.