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 nano-probes 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 micro-tumor identification.Imaging plays a critical role in overall cancer management; in diagnostics, staging, radiation planning and evaluation of treatment efficiency. Standard clinical imaging modalities such as CT, MRI and ultrasound, can be categorized as structural imaging modalities; they are able to identify anatomical patterns and to provide basic information regarding tumor location, size and spread based on endogenous contrast. However, these imaging modalities are not efficient in detecting tumors and metastases that are smaller than 0.5 cm, and they can barely distinguish between benign and cancerous tumors 1 .Molecular imaging is an emerging field that integrates molecular biology with in vivo imaging, in order to gain information regarding biological processes and to identify diseases based on molecular markers, which usually appear before the clinical presentation of the disease. Currently, positron emission tomography and single photon emission tomography are the main molecular imaging modalities in clinical use, however, they provide only functional information regarding molecular processes and metabolites, which is indirect and nonspecific to distinct cells or diseases 2,3 . Recently, various types of targeted nano-probes have been developed for optical and MRI molecular imaging, such as superparamagnetic nanoparticles 4-7 ; quantum dots [8][9][10] and gold nanoparticles as cancer optical imaging probes [11][12][13] .

Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity

“…Our extensive in vivo studies (in mice, pigs, and dogs) have confirmed that gold nanoparticles (AuNPs) show significantly higher x-ray absorption characteristics than iodinated CT agents (8,9,14,15). Recently, Kopelman and co-workers have demonstrated the feasibility of using targeted AuNPs embedded in cancer cells for CT imaging under in vitro conditions (16). Despite considerable progress achieved to date toward the development of target-specific AuNPs for use in early cancer detection, a vast majority of these systems perform well only under in vitro profiles and fail to maintain target specificity/efficacy under in vivo conditions (17).…”

An x-ray fluorescence imaging system for gold nanoparticle detection

“…Furthermore, NPs can be attached to antibodies to actively target key tumour characteristics in order to inform treatment options and prognosis (Popovtzer et al 2008, Jiao et al 2011.…”

Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis

“…Macrophages are known as 'big eaters', that phagocytose nanomaterials like GNP with high rate [86]. The GNP have long been used in the detection and imaging of biological processes and diseases [46,47,61,62,70,87]. The broad range of GNP applications is based on their unique chemical and physical properties and, in particular, on their optical properties from the visible to the IR region, depending on the particle size, shape, and structure [88,89].…”