Utilization of nanoparticles as X-ray contrast agents for diagnostic imaging applications

Among all the diagnostic imaging modalities, X-ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X-ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X-ray imaging. To date, clinically used X-ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X-ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X-rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X-ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X-ray contrast agents are discussed and the parameters that influence the efficacy of X-ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine-free NP-based X-ray contrast agents are then provided, emphasizing the studies performed to evaluate their X-ray attenuation capabilities and their toxicity in vitro and in vivo.