1 SCIENTIFIC REPORTS | (2018) 8:16561 | DOI:10.1038/s41598-018-34925-3 www.nature.com/scientificreports Localising functionalised gold- nanoparticles in murine spinal cords by X-ray fuorescence imaging and background-reduction through spatial fltering for human-sized objects Florian Grüner 1 , Florian Blumendorf 1 , Oliver Schmutzler 1 , Theresa Staufer 1 , Michelle Bradbury 2 , Ulrich Wiesner 3 , Tanja Rosentreter 4,12 , Gabriele Loers 5 , David Lutz 5 , Bernadette Richter 6 , Markus Fischer 6 , Florian Schulz 7 , Swantje Steiner 8 , Martin Warmer 9 , Anja Burkhardt 9 , Alke Meents 10 , Matthew Kupinski 11 & Christoph Hoeschen 12 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 ofering very high sensitivity, temporal and spatial resolution, large depth penetration, and arbitrarily long serial measurements. X-ray fuorescence imaging could ofer 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 fltering 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 specifc 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. Terapeutic approaches to pathological disorders would beneft strongly from high-resolution/high-sensitivity in vivo imaging and/or pharmacokinetic information. There has been a tremendous surge in both molecularly-targeted probe and device technologies for nanomedicine, which promise to enable earlier, more sensitive and precise detection for various pathologies 1–4 . For example, as a result of the aging of the human 1 Universität Hamburg and Center for Free-Electron Laser Science, Luruper Chaussee 149, 22761, Hamburg, Germany. 2 Department of Radiology and Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, New York, 10065, United States. 3 Department of Materials Science and Engineering, Cornell University, Ithaca, New York, 14850, United States. 4 Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Radiation Protection, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany. 5 Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. 6 Hamburg School of Food Science, Institute of Food Chemistry, University of Hamburg, Grindelallee 117, 20146, Hamburg, Germany. 7 Institut für Physikalische Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany. 8 University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. 9 Photon Science, DESY, Notkestraße 85, 22607, Hamburg, Germany. 10 Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany. 11 College of Optical Sciences, The University of Arizona 1630 E. University Blvd, Tucson, AZ, 85719, United States. 12 Institute for Medical Technology, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, 39106, Magdeburg, Germany. Correspondence and requests for materials should be addressed to F.G. (email: forian.gruener@uni-hamburg.de) Received: 18 April 2018 Accepted: 26 October 2018 Published: xx xx xxxx OPEN