WE-C-217BCD-07: Best in Physics (Joint Eyiaging-Therapy) - Direct Imaging of the Uptake of Platinum Anticancer Agents Using X-Ray Stimulated Fluorescence: A Proof-Of-Concept Study.

Abstract

Platinum-based (Pt) chemotherapy has greatly improved the initial response rate of different cancers. However, relapse of a drug-resistant tumor occurs with a high frequency, resulting in poor long term survival. The most common phenotype of Pt chemoresistance is decreased Pt drug accumulation in the tumor region due to either decreased influx or increased efflux, which is invisible for current imaging modalities. The inability of imaging methods to directly image the Pt drug uptake has resulted in a very unfavorable scenario for early assessment of chemotherapeutic efficacy as well as for personalized treatment planning. In this study, we investigated the feasibility of imaging the uptake and retention of Pt drugs using x-ray stimulated fluorescence CT (XSF-CT). Pt is a high atomic number element, and it emits XSF photons when excited by ionizing photons. Therefore, the alteration of spatial distribution and concentration of Pt drugs in the cancer region could be monitored with XSF-CT. In this study, a polychromatic X-ray source was used to stimulate emission of XSF photons from the Pt drugs. XSF-CT used a first-generation CT geometry. The data were collected using a cadmium telluride detector to sort out a set of spectra. The spectra were then used to generate sinogram. The bio distribution and concentration of each element were reconstructed with the ML-EM algorithm. The reconstructed images clearly identified the distributions of cisplatin. A good linearity between XSF intensities and the concentrations of cisplatin was also observed, suggesting that XSF-CT is capable of quantitative imaging. The X-ray dose for stimulating the XSF photon was 0.25 cGy per projection. XSF-CT has the potential to be a promising modality for monitoring the intervention processes within X-ray scanners. It would afford a powerful way to reliably modify an ineffective treatment regimen in nearly real time. This work was supported by NIH/NCI grants (CA133474, CA153587), an NSF grant (0854492) and a grant from the Friends for an Earlier Breast Cancer Test Foundation.