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.

An x-ray fluorescence imaging system for gold nanoparticle detection

“…This study has demonstrated the capability of the system to image GNP distribution and to distinguish between GNP concentrations. There is a strong potential that this technique can be extended to quantitative imaging, as this system has already demonstrated ability for quantitative measurement to within ± 0.005 mgAu ml −1 at low concentrations (between the detection limit of 0.001 mgAu ml −1 and 0.1 mgAu ml −1 ) (Ricketts et al 2012). Figures 7 and 8 also demonstrate that both XRF imaging systems can be used to image GNP concentrations as low as 0.025 mgAu ml −1 .…”

“…Lower concentrations were not tested in this study due to restrictions on acquisition time at the synchrotron source. However it can be inferred from previous detection limit measurements that the step and shoot system may be sensitive to even lower concentrations (Ricketts et al 2012). The addition of polycapillary optic technology will impact on the achievable sensitivity and detection limit in the following ways.…”

“…We have previously demonstrated the usefulness of this technique for this application; the accuracy of concentration measurement was found to improve by 71% on performing the scatter correction (Ricketts et al 2012). Correction involved normalizing to the image obtained using the integral counts of a region of interest covering the coherent scatter peak of each spectrum.…”

Development of XFCT imaging strategy for monitoring the spatial distribution of platinum‐based chemodrugs: Instrumentation and phantom validation

“…[17][18][19] Monochromatic beams produced with synchrotron sources are known to give higher contrast for K-shell XRF signal than clinical polychromatic x-ray sources. 20 A quasimonochromatic x-ray beam obtained from proper conversion of a clinical polychromatic x-ray beam will help to improve the current detection limit of platinum drugs by shifting Compton scattering peaks (background noise) away from the signals of interest, i.e., the K-shell platinum XRF peaks, in the acquired energy spectrum. 19,21,22 Imaging time could be a major concern in the current design using a first-generation CT geometry because the beams are acquired sequentially.…”

Fluorescence-based knife-edge beam diameter measurement to characterize X-ray beam profiles in reflection geometry

“…Energy-dispersive X-ray fluorescence (ED-XRF) has become a measurement technique widely applied to many fields such as medicine, environment, geology and cultural heritage [1][2][3][4][5]. Nowadays, both laboratory and in-field XRF apparatus are operated daily, and handheld instruments are extensively used.…”