X-ray-Fluorescence Imaging for In Vivo Detection of Gold-Nanoparticle-Labeled Immune Cells: A GEANT4 Based Feasibility Study

Abstract

The growing field of cellular therapies in regenerative medicine and oncology calls for more refined diagnostic tools that are able to investigate and monitor the function and success of said therapies. X-ray Fluorescence Imaging (XFI) can be applied for molecular imaging with nanoparticles, such as gold nanoparticles (GNPs), which can be used in immune cell tracking. We present a Monte Carlo simulation study on the sensitivity of detection and associated radiation dose estimations in an idealized setup of XFI in human-sized objects. Our findings demonstrate the practicability of XFI in human-sized objects, as immune cell tracking with a minimum detection limit of 4.4 × 105 cells or 0.86 μg gold in a cubic volume of 1.78 mm3 can be achieved. Therefore, our results show that the current technological developments form a good basis for high sensitivity XFI.

Enabling X-ray fluorescence imaging for in vivo immune cell tracking

“…In contrast, estimating the number B is non-trivial. In 11 , 12 we have presented a solution for determining and minimizing B , however, this method only works in case of human-sized objects, i.e., when the object size is a multiple of the mean free path length of the incident photons. In this work, we focus on preclinical research with mouse-sized objects.…”

Review of Development and Recent Advances in Biomedical X-ray Fluorescence Imaging

“…Taking these main factors into account, the strong anisotropy of the Compton background can be explained and used for a pixel selection algorithm. Based on this finding, in [ 24 ], a numerical study demonstrates the practicability of XFI in human-sized objects, as immune cell tracking with a minimum detection limit of 4.4 × 10 5 cells or 0.86 g of gold in a cubic volume of 1.78 mm 3 can be achieved [ 25 ].…”

“…A comparison of the XFI setup presented in [ 25 ] with currently available clinical molecular imaging methods reveals the up- and down-sides of the proposed setup. A clear advantage when comparing XFI to PET/SPECT is the achievable spatial resolution in the mm-range, which is only limited by the size of the incident X-ray beam in XFI, whereas physical limits such as a-collinearity and positron range do exist in PET [ 26 ], leading to typical resolution values between 5 and 10 mm [ 25 ].…”

Assessing Cellular Uptake of Exogenous Coenzyme Q10 into Human Skin Cells by X-ray Fluorescence Imaging

“…X-ray fluorescence (XRF) imaging meets all the major requirements for highly scientific evaluations and insights into specific modes of action: high spatial resolution (down to the nanometer scale), high sensitivity (detection of elements down to fg/cell-levels), as well as temporal resolution. The latter is of the highest relevance, because the markers applied do not decay over time, such as in single-photon emission computed tomography (SPECT) imaging or positron emission tomography (PET) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”

“…PET/SPECT are inappropriate for single-cell assessments with sub-cellular spatial resolution, and in contrast with the commonly used method of inductively coupled plasma-mass spectrometry (ICP-MS) [ 12 ], XRF is non-destructive and thus well suited even for in vivo longitudinal studies [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Finally, dedicated spatial filtering enables the possibility of overcoming the major challenge of intrinsic multiple Compton scattering when translating XRF from in vitro to large study objects, such as human organs or humans [ 4 , 8 ].…”