In the present study the applicability of x-ray fluorescence tomography for in-vivo medical imaging was investigated with respect to signal strength, background distribution and minimum detectable concentration. Tomographic imaging of the concentration distribution of suitable marker substances by the detection of the x-ray fluorescence emitted upon external excitation with x-rays has been demonstrated by other groups. However, most of these studies work with parameters that are not realistic for the medical in-vivo imaging of marker substances based on this principle; e.g. they use very small phantoms or gaseous markers.The investigated scenario uses the irradiation during a transmission computed tomography (CT) scan for the external activation of a suitable type and concentration of an x-ray fluorescence marker administered to the patient. During the irradiation, collimated and energy-resolving detectors acquire fluorescence radiation signals emitted along lines through the patient. By tomographic reconstruction of the fluorescence signal data-set, a concentration map of the marker is generated. This fluorescence image will be inherently co-registered with the high-resolution transmission CT image and can show functional or metabolic processes as an additional channel of information.The present study is based both on phantom experiments in a dedicated measurement set-up and on simulations, using various marker substances and detection concepts. Special focus was given to background reduction strategies. Moreover, the background signal in the spectral detection windows that limits the concentration resolution of the method was quantified. Signal-to-background ratios and minimum detectable marker concentrations for different scanner concepts will be presented.