Spectral Photon-Counting Molecular Imaging for Quantification of Monoclonal Antibody-Conjugated Gold Nanoparticles Targeted to Lymphoma and Breast Cancer: An In Vitro Study.

Mahdieh Moghiseh,John G. Lewis,Nigel Anderson,Dhiraj Kumar,Chiara Lowe,Aamir Raja,Anthony Butler

doi:10.1155/2018/2136840

Mahdieh Moghiseh, John G. Lewis + Show 5 more

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https://doi.org/10.1155/2018/2136840

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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.

Highlights

Mahdieh Moghiseh,1 Chiara Lowe,1 John G
Raji cells were incubated with monoclonal antibody-labelled gold, rituximab, and trastuzumab; Herceptin dilution receptor 2 (HER2)-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab, and rituximab. e calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT
Cell-based Enzyme-Linked Immunosorbent Assay (ELISA) studies on immobilised confluent HER2-positive human breast cancer cells (SKBR3) showed higher responses with the Herceptin, antihuman IgGFc-biotin, and streptavidin peroxidase combination compared with the biotinylatedHerceptin and streptavidin peroxidase combination (open and closed triangles, respectively, in Figure 1(b)). e trastuzumab and rituximab controls are shown in Figures 1(a) and 1(b) and show that the two antibodies can clearly be distinguished in a crossover study

Summary

Introduction

Mahdieh Moghiseh ,1 Chiara Lowe ,1 John G. Ese results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify speci c monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. 1. Introduction e current molecular imaging modalities, such as positron emission tomography (PET), single-photon emissioncomputed tomography (SPECT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT), have come a long way towards the observation of biological processes at molecular and cellular levels. Introduction e current molecular imaging modalities, such as positron emission tomography (PET), single-photon emissioncomputed tomography (SPECT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT), have come a long way towards the observation of biological processes at molecular and cellular levels Each of these modalities has its limitations that contribute to an inability in measuring speci c biomarkers of cancer in patients [1,2,3,4]. Nanoparticle-based drug delivery systems for systemic applications have significant advantages and have the potential to be more effective compared to their nonformulated, free drug counterparts, as surface chemistry allows the attachment of functional groups which recognise biological cues for improved specificity [26]

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