Dual-modality hafnium oxide nanocrystals for computed tomography and fluorescence imaging of sentinel lymph nodes

In the surgical treatment of breast cancer the primary tumour is removed together with the so-called sentinel lymph nodes (SLNs), the lymph nodes that have the highest probability of being invaded by cancer cells. The current clinical standard to identify SLNs uses a combination of 99mTc labelled nanocolloids and blue dyes. This workflow comes with downsides such as inflexible procedures, exposure to radioactivity, allergic side-reactions and long-lasting skin discoloration. Here, we develop a dual-modality imaging probe as alternative to the current standard and demonstrate the in vivo detection of SLNs in mice using X-ray computed tomography and near-infrared fluorescence. We synthesize and stabilize hafnium oxide nanocrystals in physiological buffer and attach IRDye 800CW to the surface. The SLN is selectively detected via both imaging modalities 15-30 minutes post-injection of the probe. Moreover, a comparison between the probe and 99mTc nanocolloids reveals similar lymphatic drainage while utilizing faster, cheaper and more readily available imaging infrastructure, which could facilitate clinical integration.