Synthesis and Characterization of Nanoprobes for X-Ray Fluorescence Computed Tomography (XFCT) Bio-imaging

Abstract: X-ray fluorescence computed tomography (XFCT) is an emerging biomedical imaging technique. The KTH-XFCT laboratory system offers a characteristic 24 keV emission line, and high spatial resolution (200 ?m) images. XFCT as a newly emerging modality also requires the exploration and development of suitable contrast agents. Nanomaterials have been widely used as contrast agents in many popular imaging modalities like MRI, PET, and CT. They have several advantages including long blood circulation time, high ratio of surface area to volume, and enhanced image contrast. However, the use of nanomaterials as contrast agents is limited by their biocompatibility and toxicity, which are determined by the physicochemical properties including size, morphology, surface chemistry. Therefore, the study on the synthesis and characterization of nanomaterials is an indispensable step. In this thesis, a group of elements (Y, Zr, Nb, Ru, Rh) are selected based on the X-ray K?-absorption energy, matching with the 24 keV emission line of KTH-XFCT source. Y, Zr, Nb, Ru and Rh based nanoparticles are synthesized by hydrothermal and polyol method, identified as the ceramic and metallic groups. XRF performance is demonstrated by the XFCT system. Metallic Ru and Rh nanoparticles are further selected to study the synthesis conditions and in vitro toxicity for their smaller TEM and hydrodynamic size. Surface properties are investigated to show the isoelectric point and polymer coating on the metallic nanoparticles. Morphological different Rh nanoparticles are obtained by introducing different additives during the synthesis, indicating the different cytotoxicity performance attributed to different morphologies. Silica coating is further performed on the surface of metallic and metallic nanoparticles to improve their biocompatibility. The in vitro toxicity assessment are performed on the murine macrophages and human ovarian cancer cell lines. X-ray fluorescence performance is evaluated for each nanoparticles by using soft-tissue equivalent holder and in situ small-animal imaging experiments. The results indicates the spatial resolution and detection sensitivity of the concentration of the metallic nanoparticles. In this work, we demonstrate the potential of a group selected nanomaterials as XFCT contrast agents for the first time, especially, investigate the synthesis, surface properties, in vitro toxicity as well as detection sensitivity of the metallic nanoparticles.