Emerging nanoparticle-based x-ray imaging contrast agents for breast cancer screening

Breast cancer is one of the most common types of cancer, however, preventive screening has contributed to a significant reduction in mortality over the past four decades. The first-line screening methods for breast cancer, such as mammography and tomosynthesis, are x-ray-based modalities. Unfortunately, their cancer detection rates are low in patients with dense breasts. These, and other high-risk women, are now encouraged to receive supplemental screening. The supplemental imaging methods are diverse, including ultrasound, MRI, nuclear imaging, and X-ray-based modalities such as breast CT and contrast-enhanced mammography/tomosynthesis. Due to their low cost and wide availability, x-ray-based modalities see significant clinical use worldwide. These techniques benefit from the use of contrast agents, which are currently iodinated small molecules designed for other purposes. Consequently, developing new contrast agents that are specifically for breast cancer screening is of interest. This review describes these modalities and the nanoparticle-based contrast agents being researched for their enhanced performance. The relevant parameters for nanoparticle-based contrast agent design are evaluated, including contrast generation and potential biointeractions. Iodinated agents are discussed for comparison. Nanoparticles covered include silver sulfide, silver telluride, gold, and bismuth sulfide-based agents, among others. Finally, perspectives on future developments in this field are offered.