Motexafin-gadolinium taken up in vitro by at least 90% of glioblastoma cell nuclei.
OBJECTIVE
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.


METHODS
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.
De Stasio
Gelsomina
G
Department of Physics and Synchrotron Radiation Center, University of Wisconsin-Madison, Stoughton, Winconsin 53589, USA. pupa@src.wisc.edu
Rajesh
Deepika
D
Ford
Judith M
JM
Daniels
Matthew J
MJ
Erhardt
Robert J
RJ
Frazer
Bradley H
BH
Tyliszczak
Tolek
T
Gilles
Mary K
MK
Conhaim
Robert L
RL
Howard
Steven P
SP
Fowler
John F
JF
Estève
François
F
Mehta
Minesh P
MP
D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008665:Metalloporphyrins / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D017348:Microscopy, Electron, Scanning Transmission; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*
D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium