Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

Abstract

In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm) were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.

Keywords: biologically targeted in vivo imaging; contrast agents; functional computed tomography; gold nanoparticles; molecular imaging.

Figure 1

Characterization of gold nanoparticles (GNPs). Upper left: transmission electron microscopy image of 30 nm GNPs (scale bar 100 nm). Upper right: zeta potential measurements at the various stages of GNP coatings. Bottom: ultraviolet-visible spectroscopy of the bare GNPs, polyethylene glycol (PEG)ylated GNPs, and anti-epidermal growth factor receptor (EGFR)-coated GNPs. Abbreviations: A.U, abitrary unit; IgG, immunoglobulin G.

Figure 2

In vivo X-ray computed tomography (CT) volume-rendered images of (A) mouse before injection of gold nanoparticles (GNPs), (B) mouse 6 hours postinjection of nonspecific immunoglobulin G GNPs as a passive targeting experiment, and (C) mouse 6 hours postinjection of anti-epidermal growth factor receptor (EGFR)-coated GNPs that specifically targeted the squamous cell carcinoma head and neck tumor. The anti-EGFR-targeted GNPs show clear contrast enhancement of the tumor (C, yellow arrow), which was undetectable without the GNPs contrast agents (A, yellow arrow). CT numbers represent the average Hounsfield units (HU) of the whole tumor area. All scans were performed using a clinical CT at 80 kVp, 500 mAs, collimation 0.625 × 64 mm and 0.521 pitch size (64 detector CT scanner, LightSpeed VCT; GE Healthcare, Little Chalfont, UK).

Figure 3

Biodistribution computed tomography results of anti-epidermal growth factor receptor-coated gold nanoparticles (active) and anti-immunoglobulin G-coated gold nanoparticles (passive) in the tumor, liver, and kidney (6 hours post intravenous injection). Background is defined as the computed tomography number of the organ before injection of gold nanoparticles. Each group was comprised of three mice.