Abstract
X-ray fluorescence computed tomography (XFCT) with nanoparticles (NPs) as contrast agents shows potential for molecular biomedical imaging with higher spatial resolution than present methods. To date the technique has been demonstrated on phantoms and mice, however, parameters such as radiation dose, exposure times and sensitivity have not yet allowed for high-spatial-resolution in vivo longitudinal imaging, i.e., imaging of the same animal at different time points. Here we show in vivo XFCT with spatial resolution in the 200- [Formula: see text] range in a proof-of-principle longitudinal study where mice are imaged five times each during an eight-week period following tail-vein injection of NPs. We rely on a 24 keV x-ray pencil-beam-based excitation of in-house-synthesized molybdenum oxide NPs (MoO2) to provide the high signal-to-background x-ray fluorescence detection necessary for XFCT imaging with low radiation dose and short exposure times. We quantify the uptake and clearance of NPs in vivo through imaging, and monitor animal well-being over the course of the study with support from histology and DNA stability analysis to assess the impact of x-ray exposure and NPs on animal welfare. We conclude that the presented imaging arrangement has potential for in vivo longitudinal studies, putting emphasis on designing biocompatible NPs as the future focus for active-targeting preclinical XFCT.
Highlights
X -RAY fluorescence (XRF) computed tomography (XFCT) with nanoparticles (NPs) as contrast agents is an emerging biomedical imaging technology, presently focused on preclinical applications but with a clinical outlook
We have shown that laboratory x-ray fluorescence computed tomography (XFCT) with high spatial resolution has potential for longitudinal studies in vivo with scan times (∼1 hour) and radiation dose (
We demonstrate few-100-μm spatial resolution in vivo X-ray fluorescence computed tomography (XFCT) imaging at different time points with a Mo sensitivity down to the order of 10−2 mg/mL
Summary
X -RAY fluorescence (XRF) computed tomography (XFCT) with nanoparticles (NPs) as contrast agents is an emerging biomedical imaging technology, presently focused on preclinical applications but with a clinical outlook. It combines the penetration depth and spatial resolution generic for x-rays with the potential for molecular or functional targeting inherent to NP contrast agents. Nanoparticles have been investigated as new contrast agents in classical absorptionbased x-ray imaging such as computed tomography (CT), with passive targeting [7]–[9] as well as with actively targeted gold NPs against, e.g., lymph nodes (anti-CD4) [10] or breast tumors (HER2) [11]. Other applications of tailored NPs include drug delivery and therapy [12], [13]
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