Localising functionalised gold-nanoparticles in murine spinal cords by X-ray fluorescence imaging and background-reduction through spatial filtering for human-sized objects

利用 X 射线荧光成像和通过空间滤波减少背景来定位小鼠脊髓中的功能化金纳米粒子,以达到人体大小的物体

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作者:Florian Grüner, Florian Blumendorf, Oliver Schmutzler, Theresa Staufer, Michelle Bradbury, Ulrich Wiesner, Tanja Rosentreter, Gabriele Loers, David Lutz, Bernadette Richter, Markus Fischer, Florian Schulz, Swantje Steiner, Martin Warmer, Anja Burkhardt, Alke Meents, Matthew Kupinski, Christoph Hoesc

Abstract

Accurate in vivo localisation of minimal amounts of functionalised gold-nanoparticles, enabling e.g. early-tumour diagnostics and pharmacokinetic tracking studies, requires a precision imaging system offering very high sensitivity, temporal and spatial resolution, large depth penetration, and arbitrarily long serial measurements. X-ray fluorescence imaging could offer such capabilities; however, its utilisation for human-sized scales is hampered by a high intrinsic background level. Here we measure and model this anisotropic background and present a spatial filtering scheme for background reduction enabling the localisation of nanoparticle-amounts as reported from small-animal tumour models. As a basic application study towards precision pharmacokinetics, we demonstrate specific localisation to sites of disease by adapting gold-nanoparticles with small targeting ligands in murine spinal cord injury models, at record sensitivity levels using sub-mm resolution. Both studies contribute to the future use of molecularly-targeted gold-nanoparticles as next-generation clinical diagnostic and pharmacokinetic tools.

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