SRC Users' Meeting - Synchrotron Radiation Center - University of ...

SRC Users' Meeting - Synchrotron Radiation Center - University of ... SRC Users' Meeting - Synchrotron Radiation Center - University of ...

23.07.2014 Views

SUBCELLULAR DISTRIBUTION OF MOTEXAFIN GADOLINIUM IN TUMOR CELLS M. J. Daniels 1 , R. J. Erhardt 1 , B. H. Frazer 1 , D. Rajesh 2 , S. P. Howard 2 , M. P. Mehta 2 , G. De Stasio 1 1 UW-Madison-SRC, 3731 Schneider Dr., Stoughton WI, 53589 2 Department of Human Oncology, Medical School UW-Madison, Madison WI 53792 Gadolinium Neutron Capture Therapy (GdNCT) is a brain cancer therapy at the experimental stages. It requires that Gd target the nuclei of cancer cells, while sparing those of healthy tissue. In our multi-year quest for the optimum Gd compound to use for this therapy, we recently tested Motexafin gadolinium (MGd). MGd is an agent with known tumor specificity, as revealed by MRI, proposed as a radiosensitizer. Macroscopic tumor uptake of MGd has been well documented, but the microscopic, subcellular distribution of MGd is not well known. We studied the subcellular distribution of MGd in two different in vitro cell lines, TB10 and U87 (both human glioblastoma cells) using the Spectromicroscope for PHotoelectron Imaging of Nanostructures with X-rays (SPHINX) at SRC. Our extensive data analysis revealed that 86% of the cell nuclei contained Gd. This result is promising because we previously calculated that an effective GdNCT agent must target >90% of cell nuclei. Furthermore, this studied showed that the concentration of Gd was highest in the cytoplasm, than the nucleus, but with longer exposure times this nuclear Gd concentration seemed to increase.

X-RAY PHOTOELECTRON EMISSION SPECTROMICROSCOPY REVEALS THAT POLYSACCHARIDES TEMPLATE ASSEMBLY OF BIOGENIC NANOSCALE CRYSTAL FIBERS G. De Stasio 1 , C.S. Chan 2 , S.A. Welch 3 , M. Girasole 4 , B.H. Frazer 1 , M. Nesterova 5 , L.M. Weise 1 and J.F. Banfield 2 (1) UW-Madison (2) UC-Berkeley (3) Australian National University (4) Italian National Research Council Neutrophilic iron oxidizing bacteria extract metabolic energy from iron oxidation in various environments, such as groundwater seeps, streams, wetlands, the rhizosphere, and hydrothermal vents. Their physiology is not well understood, and in particular the role of extracellular polymers in iron oxide mineralization and possibly energy metabolism. Recent experiments with the Spectromicroscope for PHotoelectron Imaging of Nanostructure with X-rays (SPHINX) on precipitated Fe oxides in biofilms clarified that microbially extruded polysaccharide filaments provide the precipitation substrate for amorphous FeOOH. Upon aging the mineralized filaments crystallize to ferrihydrite (2-line FeOOH), with one curved pseudo-single crystal of akaganeite (-FeOOH), at the core of each filament, of aspect ratio 1:1000:1. Structure and morphology of this unusual and unprecedented nanoscale crystal is therefore templated by polysaccharides. After formation of the crystal fiber, the polysaccharide structure is also altered, and C1s spectra suggest that the COO - group is involved in the templation mechanism.

SUBCELLULAR DISTRIBUTION OF<br />

MOTEXAFIN GADOLINIUM IN TUMOR CELLS<br />

M. J. Daniels 1 , R. J. Erhardt 1 , B. H. Frazer 1 , D. Rajesh 2 ,<br />

S. P. Howard 2 , M. P. Mehta 2 , G. De Stasio 1<br />

1 UW-Madison-<strong>SRC</strong>, 3731 Schneider Dr., Stoughton WI, 53589<br />

2 Department <strong>of</strong> Human Oncology, Medical School UW-Madison, Madison WI 53792<br />

Gadolinium Neutron Capture Therapy (GdNCT) is a brain cancer therapy at the<br />

experimental stages. It requires that Gd target the nuclei <strong>of</strong> cancer cells, while sparing those <strong>of</strong><br />

healthy tissue. In our multi-year quest for the optimum Gd compound to use for this therapy, we<br />

recently tested Motexafin gadolinium (MGd). MGd is an agent with known tumor specificity, as<br />

revealed by MRI, proposed as a radiosensitizer. Macroscopic tumor uptake <strong>of</strong> MGd has been<br />

well documented, but the microscopic, subcellular distribution <strong>of</strong> MGd is not well known. We<br />

studied the subcellular distribution <strong>of</strong> MGd in two different in vitro cell lines, TB10 and U87<br />

(both human glioblastoma cells) using the Spectromicroscope for PHotoelectron Imaging <strong>of</strong><br />

Nanostructures with X-rays (SPHINX) at <strong>SRC</strong>. Our extensive data analysis revealed that 86% <strong>of</strong><br />

the cell nuclei contained Gd. This result is promising because we previously calculated that an<br />

effective GdNCT agent must target >90% <strong>of</strong> cell nuclei. Furthermore, this studied showed that<br />

the concentration <strong>of</strong> Gd was highest in the cytoplasm, than the nucleus, but with longer exposure<br />

times this nuclear Gd concentration seemed to increase.

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