Spectral Photon-Counting Molecular Imaging for Quantification of Monoclonal Antibody-Conjugated Gold Nanoparticles Targeted to Lymphoma and Breast Cancer: AnIn VitroStudy

Abstract

The purpose of the present study was to demonstrate an in vitro proof of principle that spectral photon-counting CT can measure gold-labelled specific antibodies targeted to specific cancer cells. A crossover study was performed with Raji lymphoma cancer cells and HER2-positive SKBR3 breast cancer cells using a MARS spectral CT scanner. Raji cells were incubated with monoclonal antibody-labelled gold, rituximab (specific antibody to Raji cells), and trastuzumab (as a control); HER2-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab (specific antibody to HER2-positive cancer cells), and rituximab (as a control). The calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT. Spectral imaging results showed that the Raji cells-rituximab-gold and HER2-positive cells-trastuzumab-gold had a quantifiable amount of gold, 5.97 mg and 0.78 mg, respectively. In contrast, both cell lines incubated with control antibody-labelled gold nanoparticles had less gold attached (1.22 mg and 0.15 mg, respectively). These results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify specific monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. The present study reports the future potential of spectral molecular imaging in detecting tumour heterogeneity so that treatment can be tuned accordingly, leading to more effective personalised medicine.

Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

“…Spectral photon-counting CT could enable a more sensitive and specific research tool. Functionalized or labelled high-Z nanoparticles with spectral CT has been demonstrated [23,26]. Disease severity, disease heterogeneity, and drug delivery could be measured [26].…”

“…Functionalized or labelled high-Z nanoparticles with spectral CT has been demonstrated [23,26]. Disease severity, disease heterogeneity, and drug delivery could be measured [26]. With regards to drug development, translational research using preclinical micro-CT plays a pivotal role in the management of TB, by assessing disease severity and evaluating new effective anti-tuberculosis drug combinations for therapy [35,45,46].…”

“…Photon energy measurements, combined with known attenuation energy dependence in different materials, result in the simultaneous differentiation and quantification of up to six materials [15,20]. Spectral photon-counting CT imaging with the MARS scanner has proven useful in a wide range of preclinical applications pertinent to common human conditions, including crystal arthropathies [21], atherosclerosis [22], bone health [23,24,25], and cancer [26,27]. Studies have also used MARS spectral imaging to investigate novel targeted pharmaceuticals, such as hafniabased nanoparticles that have been chemically trained to highlight bone microdamage [23,26].…”

“…Spectral photon-counting CT imaging with the MARS scanner has proven useful in a wide range of preclinical applications pertinent to common human conditions, including crystal arthropathies [21], atherosclerosis [22], bone health [23,24,25], and cancer [26,27]. Studies have also used MARS spectral imaging to investigate novel targeted pharmaceuticals, such as hafniabased nanoparticles that have been chemically trained to highlight bone microdamage [23,26]. To demonstrate how spectral photon-counting CT can facilitate drug dose optimization via molecular imaging, an iodine-based contrast agent was administered to a murine model of TB and scanned using a spectral photon-counting CT scanner.…”

CdTe Based Energy Resolving, X-ray Photon Counting Detector Performance Assessment: The Effects of Charge Sharing Correction Algorithm Choice

“…Further, due to its photon counting nature, x-CSI promises to produce images free from electronic noise [4] that can be used to derive quantitative spectral information rather than just qualitative data with a greater accuracy and less noise than dual energy CT [5]. This opens the possibility that X-ray systems will be able to move beyond the largely structural images they currently deliver and additionally enter the field of molecular imaging [6,7]. The ability of an x-CSI detector to do this will depend on how efficiently it can absorb incident photons and how accurately it can resolve their energy.…”