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Simple Summary  One novel approach in cancer therapy is the use of genetically modified immune cells that are more specifically directed to a tumor than common chemotherapy. This creates the need for medical imaging methods that can be used to track these immune cells during therapy. Our study provides computer simulations of potential applications of X-ray fluorescence imaging for this purpose. We showed that if immune cells were labeled with gold nanoparticles as an imaging marker, the amounts of immune cells that would be expected to be found in a tumor or inflammation site could be detected with our setup. Our feasibility study thus shows results that are promising estimates on what can be achieved.    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 × 10 5  cells or 0.86 μg gold in a cubic volume of 1.78 mm 3  can be achieved. Therefore, our results show that the current technological developments form a good basis for high sensitivity XFI.

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