Abstract The goal of this proposed project is to develop an ultrahigh sensitivity, broadband X-ray fluorescence emission tomography (XFET) system. This system combines advanced CdTe X-ray imaging spectrometers assembled in a customized SPECT-like detection system design, and optimized source/filtering configurations to achieve a dramatically improved sensitivity to a broad range of metal elements that emit fluorescence x-rays of 5-100 keV. This system would be ideally suited for imaging heavier elements, such as Hf, Gd, Au and Pt with adequate tissue penetration for in vivo small animal studies. As a design target, we seek to construct an XFET system that is capable of imaging these heavy metals at a concentration of the order of 10 µg/ml in tissue equivalent, mouse-sized objects irradiated with X-ray sources of ~10 mA tube current and up to 150 kVp, and with an imaging time of around 1-2 hours and at a spatial resolution of a few hundred microns. This system would offer a unique imaging tool for guiding and monitoring the delivery of radiation-induced and nanoparticle-mediated radiation therapy.