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.
Highlights
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
Population, cancer is the most common cause of death worldwide, and secondary prevention methods, directed at early cancer/metastases detection, will improve the likelihood of successful therapy and higher survival rates[5]. Another opportunity to foster the development of targeted therapy is in vivo tracking of medical drugs through the body, based e.g. on antibody reactions, i.e. pharmacokinetic (PK) studies[6,7,8]. One such promising non-invasive imaging solution is based on X-ray fluorescence imaging (XFI) of gold-nanoparticles (GNPs), which are either functionalised or bound to medical drugs
This resolution is roughly equivalent to that offered by clinical Magnetic Resonance Imaging (MRI), but higher than that associated with clinical Positron Emission Tomography (PET) scanners; the latter modality has a typical clinical resolution of 4–5 mm
Summary
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. 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. Population, cancer is the most common cause of death worldwide, and secondary prevention methods, directed at early cancer/metastases detection, will improve the likelihood of successful therapy and higher survival rates[5] Another opportunity to foster the development of targeted therapy is in vivo tracking of medical drugs through the body, based e.g. on antibody reactions, i.e. pharmacokinetic (PK) studies[6,7,8]. The XFI-approach has been under investigation for quite some time[9,10,11,12,13,14,15], most approaches still suffer from this intrinsic “background problem” for human-sized objects at tolerable dose-levels, when the GNP-amounts are as low as expected for clinical applications and/or reported from small-animal studies
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