Real-time Dosimetry Imaging of Nanoparticle-Mediated Radiation Therapy with Integrated X-ray Luminescence and X-ray Fluorescence Imaging

364 Objectives: Photodynamic therapy’s (PDT) enhances the localization of cancer therapy by using external optical photons to activate nanoparticles’ (NP) production of cytotoxic singlet oxygen [1]-[4]. X-ray induced photodynamic therapy (X-PDT) uses more penetrating X-rays to stimulate NPs into producing light, via X-ray luminescence (XL), which a photosensitizer then converts to singlet oxygen, allowing therapeutic effects to reach greater depths [2], [5]-[8]. The X-ray luminescence (XL) production during X-PDT can be correlated to singlet oxygen yield and its therapeutic effect; also, the characteristic X-rays produced via X-ray fluorescence (XF) by the metals in the NPs provide high resolution spatial biodistribution information. Thus, these XF and XL emissions would allow for concurrent monitoring of the therapeutic delivery and distribution. In this work, an integrated imaging platform will examine the therapeutic delivery of LiGa5O8:Cr and KI NPs in vitro by monitoring XL and XF emissions [8]. The therapeutic efficiency’s dependence on incident X-ray energy will be examined, and the system will conduct a phantom study to determine its spatial resolution and sensitivity. Methods: To understand the incident X-ray energy’s effect on cell cytotoxicity, various incident X-ray beam energy profiles will irradiate cancer cell cultures loaded with the NPs. The incident X-ray beam profile is collimated to 100 μm FWHM pencil beam and either produced by filtering a 50 kVp polychromatic source or through a 17.48 keV monochromatic Mo source. An Amptek XR-100T CdTe detector measures these incident profiles and the profiles of the beam attenuated by the sample, providing information on the energy removed by the sample (which can be correlated to dose). To verify the effect of various X-ray irradiation strategies on reactive oxygen species generation, singlet oxygen sensor green, SOSG, will be placed in the cell cultures allowing for real time information on the cytotoxicity produced upon irradiation by measuring the SOSG’s visible light emissions with an Andor iXon 887 EMCCD camera, coupled to a demagnifying tube. The camera can also directly measure the XL signals produced by the NPs. The NPs’ production of XF will also be collected by an Andor iKon-L 936 CCD, which is coupled to a multi-slit aperture and positioned perpendicular to the beam. Correlations between these measured signals and cell viability will determine which irradiation schemes are most dose-effective for therapy. Lastly, the system, depicted in Fig. A, will conduct a phantom study to examine system sensitivity and resolution for imaging these nanoparticles. Results: Fig. B demonstrates the LiGa5O8:Cr’s capability of inducing cytotoxicity upon irradiation at given dosages allowing for incident energy optimization study [8]. Preliminary studies were conducted by imaging a 3-mm diameter NMR tube containing Y2O3:Eu3+ NPs inserted in a 5-mm tube containing NaBr superficially attached to a mouse phantom that was irradiated by the polychromatic source of various filter configurations. Fig. C shows the XL signal produced per keV attenuated by Y2O3:Eu3+ NPs for these filtered configurations while Fig. D shows the XF equivalent. Fig.E shows a combined XF/XL image with the XL (blue) and the bromide’s XF Kα1 signal (red). Fig.F shows a combined XF image with the yttrium Kα1 XF (green), the bromide Kα1 (red), and the scattered incident X-rays (blue). Lastly, Fig.G shows a 3D image depicting XF/XL and CT of the mouse phantom with yttrium XL (red), bromide XF (green), and scattering (blue). Conclusions: The initial results showed the integrated system’s potential for imaging and monitoring X-PDT XL and XF emissions during NP irradiation. The initial results also show that NPs’ the dose-effectiveness of XL and XF emission depend on incident X-ray energy. Future work will examine these correlations for the LiGa5O8:Cr and KI NPs using the imaging platform.