A Multi-Contrast X-ray Fluorescence, X-ray Luminescence and X-ray CT Functional Imaging Platform for In Vivo Imaging of Non-Radioactive Therapeutic Agents in Small Animals

1760 Objectives: The clinical use of the metal-based anti-tumor drug, cisplatin, has waned since its discovery in 1965 due to the serious side effects such as myelosuppression, nephrotoxicity, neurotoxicity, and increasing drug resistance after recurrent treatments [1]-[5]. Thus researchers have begun investigating utilizing other metals, such as hafnium and gold, for radioenhancement [6], [7]. For instance, Dr. Wenbin Lin has developed radiosensitizers based on a nanoscale metal-organic framework (NMOF) containing hafnium for X-ray induced photodynamic therapy (X-PDT), which converts incoming X-ray irradiation into visible light through X-ray luminescence (XL), which in turn is converted to cytotoxic singlet oxygen via a conjugated photosensitizer [8]. However, the biological behavior and pharmacological mechanism of these metallodrugs are poorly understood due to the intrinsically complex nature of the human body. In this presentation, we report a recently developed functional X-ray imaging platform for imaging a wide range of metals in both tissue samples and small lab animals and present X-ray fluorescence (XF) and X-ray luminescence (XL) imaging of several metallodrugs in mouse phantoms. Methods: The Design of the XFCT/XLCT Functional Imaging Platform. Fig. A shows our XLCT/XFCT imaging platform where the X-ray luminescence signal is collected byan Andor iXon 887 EMCCD coupled to a demagnifying tube and then a Zeiss lens coupled to band-pass optical filters, and the X-ray fluorescence signal is collected by an Andor iKon-L DO936 direct-conversion CCD camera consisting of a 2048 by 2048 array of 13.5 μm square pixels. The upgraded system that we will discuss in this presentation is shown in Fig. B, where the CCD camera is replaced by a half-ring of HEXITEC CdTe detector modules to cover a wider X-ray energy range of 5 keV to 120 keV and provide a spatial resolution of 250 μm. Each detector module of 2 cm x 2 cm is coupled to a multiple-slit aperture of 100-300 μm width that runs perpendicular to the incident X-ray beam. The system contains two X-ray sources: a filterable 50 kVp polychromatic source and a 17.4 keV monochromatic source. From these sources and filtering, an optimized incident X-ray energy can be selected to efficiently produce XL or XF in the sample.Imaging Studies: A plastic mouse phantom containing four 400 μm diameter channels each filled with Y2O3:Eu3+ nanoparticles, LaF3:Tb3+ nanoparticles, HfO2 nanoparticles and cisplatin. Both the Y2O3:Eu3+ and LaF3:Tb3+ nanoparticles are capable of both XF and XL emissions while cisplatin and HfO2 would only produce XF. Therefore, a multiplexed XF/XL image can be produced from this sample. Additionally, a resolution phantom containing LaF3:Tb3+nanoparticles will also be imaged using both XF and XL and coregistered together. The system’s resolution and sensitivity for both the XF and XL imaging of this agent will also be examined and presented. Results: Fig C shows a multi-isotope spectrum consisting of 241Am, 57Co, and 99mTc acquired using a HEXITEC detector. For the 122 keV peak of Co57, an 0.75 % energy resolution was observed. The preliminary system successfully acquired tri-modal images with Fig. D-F co-registered with a CT image. The sample is an 8-mm diameter gel phantom containing three 600 μm diameter channels of Y2O3:Eu3+ NPs. The images obtained include XF slice with the energy selected for the 14.96 keV K­α1 peak of yttrium (Fig. D), and the XL slice of the NP (Fig. E). Lastly, Fig. F shows a 3D-rendered combined image of the dual emission image. Conclusions: The preliminary results already demonstrate the potential for a dual contrast system to monitor the distribution of NPs and their therapeutic delivery through XF and XL. The upgraded system using a partial ring of HEXITEC detectors for XF detection will be presented as well as the overall imaging sensitivity and resolution of the dual contrasting imaging platform.