Trends in Molecular Medicine
ReviewFeature ReviewInorganic nanoparticle-based contrast agents for molecular imaging
Section snippets
NPs as molecular imaging agents
Molecular imaging is a new frontier of biomedical research for visualizing, characterizing and monitoring biological processes in cells, tissues and organisms using sensitive instrumentation and contrast mechanisms [1]. Molecular imaging interrogates biological processes to report on and reveal the molecular abnormalities that form the basis of diseases. As a result, molecular imaging provides a powerful tool for the diagnosis of diseases including cancer, cardiovascular syndrome and
Molecular imaging modalities
Inorganic NPs are an actively explored technology for the development of contrast agents for molecular imaging. Figure 1 and Table 1 list the types of inorganic NPs being developed as imaging agents, and Figure 1 also shows some typical examples of inorganic NP-based molecular imaging 6, 9, 13, 14, 15, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33. Before discussing the performance of these contrast agents, it will be helpful to provide a brief introduction to the imaging modalities whose
Major inorganic NPs for molecular imaging
Among the inorganic NPs displayed in Figure 1a, iron oxide NPs have been used clinically as contrast agents for MR imaging, whereas the other two have been mainly evaluated in the preclinical setting. In addition, recent advances in synthesis have produced many novel NPs with potential applications in molecular imaging, and Table 1 shows a partial list of these inorganic NPs. These and additional examples can also be found in the Molecular Imaging and Contrast Agent Database (//www.ncbi.nlm.nih.gov/
Surface modification of inorganic NPs
The surfaces of inorganic NPs often need to be modified to: i) allow transfer from a nonhydrolytic solvent into an aqueous medium; ii) increase the circulation time in the blood stream by adding a poly(ethylene glycol) (PEG) coating, or PEGylation; iii) enhance the targeting efficiency via the conjugation of binding ligands; and iv) increase functionality via the addition of other components including drugs. Three important issues must be taken into consideration when modifying the surfaces of
Delivery and targeting of inorganic NPs
NPs provide a range of advantages over molecular contrast agents traditionally used for molecular imaging. For example, the differences in vasculatures between normal and cancerous tissues enhance the accumulation of NPs in solid tumors (Figure 3a). Endothelial cells in normal tissues are well aligned and closely packed, whereas those in solid tumors are relatively leaky 81, 82, 83. Because of their large sizes, inorganic NPs circulating in the bloodstream cannot easily enter normal tissues yet
Biodistribution, clearance and the toxicity of inorganic NPs
In reality, it is impossible to have all injected NPs accumulated at the site of disease. As such, the biodistribution of inorganic NPs has to be considered and optimized from the beginning. Typically, inorganic NPs administered intravenously are mostly taken up by the liver and spleen, with the amount of accumulated particles depending on the particle size, shape and surface chemistry. There are several reports on the biodistribution of QDs, iron oxide NPs and gold colloids 57, 104, 105, 106,
Multimodal imaging with inorganic NPs
To diagnose malignancy accurately and at an early stage, it is often necessary to use a combination of different imaging modalities simultaneously. As such, there has been a strong interest in developing new imaging techniques based on optical and spectroscopic mechanisms. Notable examples include OCT, PAT, SERS and multiphoton microscopy. To keep pace with these emerging techniques, inorganic NPs need to be engineered with a variety of properties, and in some cases, they also need to enhance
Concluding remarks
Many types of inorganic NPs have been proposed and evaluated as potential contrast agents for molecular imaging, but most are still being tested in vitro or in vivo with small animals. Although a few (e.g. iron oxide NPs for MR imaging) have been approved for clinical use, most are still in development and will need to solve the potential toxicity issue. It is expected that some of the inorganic NPs (e.g. gold colloids) will overcome these hurdles and eventually move into the clinical phase. In
Acknowledgements
Our research in this field has been supported in part by an National Institutes of Health (NIH) Director's Pioneer Award (DP1 OD000798), an NIH research grant (1R01 CA138527) from the NCI and startup funds from Washington University in St. Louis.
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