X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples

Abstract

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demon-strate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach ex-trapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.

Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging—A Numerical Study

“…The software Geant4 is designed to simulate interactions of particles passing through matter using Monte Carlo methods [42,43]. Geant4-based simulations were shown to be consistent with first ex vivo and in situ experiments in previous work of our group [22,44,45] and can thus be used to explore diverse applications of XFI without the need of extensive animal research. As a result of our simulations, we intend to illuminate both prospects and challenges of implementing X-ray fluorescence in the highly topical area of cancer research to lay the foundation for future in vivo experiments.…”

X-ray-Fluorescence Imaging for In Vivo Detection of Gold-Nanoparticle-Labeled Immune Cells: A GEANT4 Based Feasibility Study

“…Moving and tilting a patient into every direction and angle is not possible, however. Therefore, more compact X-ray sources like laser-based Thomson scattering sources could be an ideal solution [60][61][62][63].…”

Research on X-ray Fluorescence Enhanced Fluoroscopy Imaging Technology

“…At present, polychromatic benchtop XFCT has been used for gold nanoparticles (GNPs) detection in a tumor-bearing mouse and shows drastically enhanced sensitivity and quantification, up to two orders of magnitude better than conventional X-ray CT [7]. X-ray fluorescence imaging of GNPs on mice has been able to achieve sub-mm spatial resolution [8], and the minimum detectable nanoparticle mass has reached 5 pg in simulations [9]. These developments are all based on GNPs [10], which also verifies our conjecture of using high-Z elements to enhance fluoroscopy imaging.…”

“…The structure of X-ray fluorescence photon imaging using chest X-ray excitation is similar to cone beam XFCT imaging, so we can learn from the XFCT de-scattering algorithm [9,11]. Investigators have also tried full-field fan-beam X-ray fluorescence computed tomography with a conventional X-ray tube and photon-counting detectors for fast nanoparticle bioimaging [12].…”