Through a series of recent studies with gold nanoparticles (GNPs), the current research team has shown that x-ray fluorescence computed tomography (XFCT), traditionally a synchrotron-based imaging modality, can be performed on a benchtop setting for small-animal-sized objects using an ordinary diagnostic energy range polychromatic x-ray source. Consequently, one can now envision a widespread use of XFCT for biomedical research, especially in light of ever-growing interest in high atomic number (Z > ~50) metal nanoparticles such as GNPs for various cancer diagnostic/therapeutic applications and preclinical testing of such applications using small animal models. Once fully developed, benchtop XFCT will offer a powerful tool to determine the biodistribution of GNPs and other metal NP probes in vivo without cumbersome and time-consuming ex vivo analysis after sacrificing animals. Moreover, it will enable seamless multimodal imaging with micro-CT (CT) in a single platform, resulting in images showing greater anatomical details while retaining all the benefits from spectroscopic quantitative imaging. Furthermore, when performed with bioconjugated/functionalized GNPs and/or other metal NP probes, benchtop CT/XFCT will provide an unprecedented multimodal/multiplexed molecular imaging option for more effective drug discovery and development. Despite significant research advances on benchtop XFCT in recent years, however, there are some critical technical challenges that must be overcome to realize these possibilities. Thus, this project brings together a team of experts from Brookhaven National Laboratory, University of Massachusetts Medical School, and The University of Texas MD Anderson Cancer Center to surmount the key technical hurdles that prevent the envisioned benchtop CT/XFCT system from being used routinely for in vivo imaging under realistic constraints. The following three specific aims will be pursued to achieve the goal of this project: (1) Design and optimization of a benchtop CT/XFCT system; (2) Development of novel high energy-resolution solid state array detectors for benchtop XFCT; (3) Investigation of multimodal/multiplexed molecular imaging capability of a benchtop CT/XFCT system. Upon successful completion, a practical benchtop CT/XFCT system will become ready for routine preclinical molecular imaging studies and further improvements. A fully-developed benchtop CT/XFCT system will offer novel imaging options that can considerably improve the efficacy of preclinical testing of NP- based diagnostic/therapeutic strategies, thereby increasing the likelihood of bringing paradigm-shifting advancements in cancer nanomedicine. A novel high energy-resolution detector system developed from this project will also offer new opportunities for a wide range of quantitative x-ray imaging applications beyond benchtop XFCT.

Public Health Relevance

The main goal of the current project is to enable routine preclinical in vivo molecular imaging with benchtop x- ray fluorescence computed tomography (XFCT) and metal nanoprobes such as gold nanoparticles (GNPs). We aim to achieve this goal by developing novel high energy-resolution pixelated detectors for the cone-beam implementation of benchtop XFCT, while further improving the sensitivity of benchtop XFCT. Upon completion of this project, a benchtop XFCT system with simultaneous micro-CT capability will enable determination of the biodistribution of GNPs (as well as other metal NPs) in vivo and also be used to perform unprecedented preclinical multimodal/multiplexed molecular imaging tasks, significantly enhancing the likelihood of bringing paradigm-shifting advancements in diagnostic/therapeutic strategies for cancers and other diseases.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Biomedical Imaging Technology B Study Section (BMIT-B)
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Shabestari, Behrouz
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University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
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