CT and X-ray contrast agents: Current clinical challenges and the future of contrast

Computed tomography (CT) is a powerful and widely used imaging technique in modern medicine. However, it often requires the use of contrast agents to visualize structures with similar radiographic density. Unfortunately, current clinical contrast agents (CAs) for CT have remained largely unchanged for decades and come with several significant drawbacks, including serious nephrotoxicity and short circulation half-lives. The next generation of CT radiocontrast agents should strive to be long-circulating, non-toxic, and non-immunogenic. Nanoparticle contrast agents have shown promise in recent years and are likely to comprise the majority of next-generation CT contrast agents. This review highlights the fundamental mechanism and background of X-ray and contrast agents. It also focuses on the challenges associated with current clinical contrast agents and provides a brief overview of potential future agents that are based on various materials such as lipids, polymers, dendrimers, metallic, and non-metallic inorganic nanoparticles (NPs). We realized a need for clarification on a number of concerns related to the use of iodinated contrast material as debates regarding the safety of these agents with patients with kidney disease, shellfish allergies, and thyroid dysfunction remain ongoing in medical practice. This review was partially inspired by debates witnessed in medical practice regarding outdated misconceptions of contrast material that warrant clarification in translational and clinical arenas. Given that conversation around currently available agents is at somewhat of a high water mark, and nanoparticle research has now reached an unprecedented number of readers, we find that this review is timely and unique in the context of recent discussions in the field.