An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles

Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging(1-8), both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots(9-12), magnetic(13) and magnetofluorescent nanoparticles(14,15), gold nanoparticles and nanoshells(16-19), among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi2S3 nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi3+), high X-ray absorption (fivefold better than iodine), very long circulation times (> 2 h) in vivo and an efficacy/safety profi comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi2S3 nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.