Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

Abstract

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R² = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R² = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.

Figure 1

(A) Schematic representation of the AuNP. (B) Transmission electron micrograph of the AuNP.

Figure 2

(A) Diagram of the phantom used. (B) SPCCT derived images (left to right: conventional CT image, water material decomposition, gold image, overlay of gold image on water image). (C) Comparison between the expected and measured concentrations. (D) Bland-Altman plot depicting the comparison of gold content between the prepared and measured concentration as determined by SPCCT image analysis.

Figure 3

(A) SPCCT images displaying the AuNP biodistribution in the liver over time (left to right: conventional CT image, gold image, overlay). Star: liver, arrowhead: aorta, chevron: bone marrow. (B) Gold content in the liver and blood at various time points, as determined from SPCCT image analysis.

Figure 4

SPCCT images displaying the AuNP retention at one month (M1) in the organs of the mononuclear phagocyte system (left to right: conventional CT image, gold image, overlay). Star: liver, head arrow: spleen, chevron: bone marrow, full arrow: lymph node.

Figure 5

Left: Abdomen SPCCT images of a rabbit at 6 months after injection of gold nanoparticles with coronal conventional CT image, center: 3D volume rendering reconstruction of the conventional HU images with segmentation of the organs of interest (dark blue: liver, light blue: spleen, green: right kidney, red: lymph nodes, light grey: bone structure), right: 3D volume rendering reconstruction of the gold images.

Figure 6

The biodistribution of AuNP among the organs of interest at several time points. Error bars represent the mean of the noise in the ROIs.

Figure 7

(A) Comparison between the expected and measured concentrations. (B) Bland-Altman plot depicting the comparison of gold content in rabbit organs as determined via ICP-OES and SPCCT image analysis.

Figure 8

Transmission electron micrographs of rabbit organs from the mononuclear phagocyte system 6 months after AuNP injection over a range of magnifications. A-C: liver, D-F: spleen, G-I: lymph node, J-L: bone marrow (H: hepatocyte, K: Kuppfer cell, L: lysosome, N: nucleus, S: sinusoid).