Rationale and Objectives
The purpose of this study was to demonstrate the application of gold nanoparticles (AuNP) as a contrast agent for a clinical x-ray computed tomography (CT) system using a phantom and juvenile swine.
Materials and Methods
A tissue-mimicking phantom with spherical inclusions containing known concentrations of Au was scanned. Swine were injected with gum Arabic stabilized Au nanoparticles (GA-AuNP), up to 85 mg kg −1 body weight. CT scans were performed before and after the injections. Changes in Hounsfield unit (HU) values between pre- and post- injection scans were evaluated and compared to postmortem determinations of Au uptake. Average uptake of GA-AuNP in the liver of the swine was 380 μg per gram of liver and 680 μg per gram of spleen.
Results
Concentrations of Au in tissues increased the CT numbers in liver by approximately 22 HU per mg Au concentration at 80 kVp and 27 HU per mg Au concentration at 140 kVp. These data were consistent with HU changes observed for similar concentrations in the phantom.
Conclusions
AuNP-based contrast agents may be useful in x-ray based CT. This study provides data for determining concentrations of AuNP in comparison to other contrast materials.
In this work, the authors have used an agarose-based phantom and juvenile swine as a model for evaluating the x-ray contrast properties of gold nanoparticles (AuNP) at low concentrations. This serves to advance our understanding of the effects of these agents and their potential for application to molecular imaging using targeted, hybrid nanoparticle agents.
This work is unique in that we have performed our studies employing the higher energy x-ray spectrum used in clinical computed tomography (CT) equipment. This provides a more realistic challenge for the gold-based nanoparticle agents as a lower photoelectric interaction is in effect at these higher energies than has been reported in earlier published results. This work also is testing the effect of relatively low concentrations of AuNP and provide some framework for expectations of the required uptake and dose to make molecular imaging possible using AuNP with targeting moieties.
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Methods and materials
Tissue-mimicking AuNP Phantom
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Swine Model
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AuNP Contrast Agent Production
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Animal Dose Protocol
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CT Imaging Protocol
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Biodistribution of AuNP
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Results
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Table 1
Summary of CT Results from Swine Subjects
Liver Spleen Subject Days in Study Dose (mg Au kg-1) AuNP uptake (μmol) ?HU @ 80 kVp ?HU @ 140 kVp AuNP uptake (μmol) ?HU @ 80 kVp ?HU @ 140 kVp A 29.00 86.00 264.21 12.50 13.3 425.26316 9.1 10.9 B 10.00 88.00 148.42 5.70 9.3 297.89474 2.24 2.79 C 10.00 99.00 187.37 7.23 7.87 356.84211 8.5 7
CT, computed tomography; Au, gold; NP, nanoparticles; HU, Hounsfield units.
Mean voxel values for each organ (measured in HU) generally increased in proportion to the Au concentration determined after necropsy. ΔHU values are determined from differences in images acquired at the beginning of the study (Day 0) and at the end of the study (# Days in study).
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Discussion
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Summary
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