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. Specific, 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 agreed with the imaging and ICP-OES in that much higher concentrations of AuNP were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT is capable of repetitive and non invasive determination of the biodistribution of gold nanoparticles in vivo.

Gold Nanoparticle Mediated Multi-Modal CT Imaging of 3 Hsp70 Membrane Positive Tumors

“…The application of gold nanoparticles for imaging in vivo is a promising new approach in the field of in vivo imaging [6,18,19]. The uptake of antibody-conjugated nanoparticles into tumor cells is dependent on different factors.…”

How can molecular micro-CT imaging revolutionize drug discovery?

“…Nanoparticles made of high Z materials (such as gold, bismuth, barium, and tungsten) are the main components of theranostic nanoparticles which can be used as the CT scan contrast agents [13]. Such nanoparticles can be easily entrapped into a nanocarrier to be accompanied by drugs or genes [9][10][11].…”

“…They can be also conjugated with various targeting agents [14]. With regard to the mentioned potentials of theranostic nanoparticles and the capabilities of CT scan imaging, we can determine the biodistribution profile of new drug formulations [13,15]. This is also a good idea for longitudinal studies with the minimum level of invasiveness and without the need to sacrifice the animals which are under examinations.…”

Effects of bisphosphonate ligands and PEGylation on targeted delivery of gold nanoparticles for contrast-enhanced radiographic detection of breast microcalcifications

“…5). This suggests that CT can be used to noninvasively measure the in vivo biodistribution of NPs, especially with the advent of photoncounting spectral CT enabling k-edge imaging [40].…”