Targeted gold nanoparticles enable molecular CT imaging of cancer

Abstract

X-ray based computed tomography (CT) is among the most convenient imaging/diagnostic tools in hospitals today in terms of availability, efficiency, and cost. However, in contrast to magnetic resonance imaging (MRI) and various nuclear medicine imaging modalities, CT is not considered a molecular imaging modality since targeted and molecularly specific contrast agents have not yet been developed. Here we describe a targeted molecular imaging platform that enables, for the first time, cancer detection at the cellular and molecular level with standard clinical CT. The method is based on gold nanoprobes that selectively and sensitively target tumor selective antigens while inducing distinct contrast in CT imaging (increased X-ray attenuation). We present an in vitro proof of principle demonstration for head and neck cancer, showing that the attenuation coefficient for the molecularly targeted cells is over 5 times higher than for identical but untargeted cancer cells or for normal cells. We expect this novel imaging tool to lead to significant improvements in cancer therapy due to earlier detection, accurate staging, and microtumor identification.

Figure 1. the first ever medical X-ray image (1895) taken by Roentgen

‘Hand with Ring’ print of Wilhelm Röntgen’s first “medical” X-ray, taken on 22 December 1895. It dramatically showed the bones of her fingers; however the real size of her finger’s soft tissue could be garnered from the clearly visible gold ring on her finger. Likewise, below we show that “ringing” the tumor cells with gold nanoparticles makes it effectively more visible to CT. Note that the size of the ring maps the width of the finger’s soft tissue. Radiology Centennial, Inc copyrighted in 1993.

Figure 2. CT attenuation (HU) of SCC head and neck cancer cells and positive and negative control samples

Bar graph with standard deviation of 3 samples; larynx and oral cancer cells that were targeted with A9 antibody coated gold nanorods (AuNR); larynx and oral cancer cells without gold nanorods; larynx and oral cancer cells targeted with nanorods that are coated with non-matching antibodies (KHRI-3); normal fibroblast and melanoma cells targeted with A9 antibodies, bare gold nanorods in water solution (2.5 mg/mL), and water.

Figure 3. Dark field microscope images of SCC head and neck cancer cells

Dark field microscope images of SCC head and neck cancer cells (oral cancer upper images, larynx cancer lower images) after incubation with non-matching antibody-coated gold nanorods (left) vs. matching UM-A9 antibody-coated gold nanorods (right). Scale bar: 10 μm