title: A quantitative x-ray detection system for gold nanoparticle tumour biomarkers.
abstract: X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach is being developed that employs x-ray fluorescence with an aim to locate heavy nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles can be functionalized to act as markers for tumour characteristics to map the disease state, with the future aim of imaging them to inform cancer therapy regimes. The uptake of functionalized nanoparticles by cancer cells will also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy-resolving silicon drift detector with high spectral resolution, shows potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A series of synchrotron measurements are presented; a linear relationship between fluorescence intensity and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1), the detection limit of the system. Successful use of a bench-top source, suitable for possible future clinical use, is also demonstrated, and found not to degrade the detection limit or accuracy of the GNP concentration measurement. The achieved system sensitivity suggests possible future clinical usefulness in measuring tumour uptake in vivo, particularly in shallow tumour sites and small animals, in ex vivo tissue and in 3D in vitro research samples.
authors.affiliation: Department of Medical Physics and Bioengineering, University College London, UK. kricket@medphys.ucl.ac.uk
authors.forename: K
authors.initials: K
authors.lastname: Ricketts
authors.forename: A
authors.initials: A
authors.lastname: Castoldi
authors.forename: C
authors.initials: C
authors.lastname: Guazzoni
authors.forename: C
authors.initials: C
authors.lastname: Ozkan
authors.forename: C
authors.initials: C
authors.lastname: Christodoulou
authors.forename: A P
authors.initials: AP
authors.lastname: Gibson
authors.forename: G J
authors.initials: GJ
authors.lastname: Royle
mesh_terms: D000042:Absorption; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism*; D006046:Gold / Q000737:chemistry* / Q000378:metabolism*; D057230:Limit of Detection; D053768:Metal Nanoparticles; D013052:Spectrometry, X-Ray Emission / Q000295:instrumentation / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D006046:Gold