Dual-Modality Hafnium Oxide Nanocrystals for in Vivo Computed Tomography and Fluorescence Imaging of Sentinel Lymph Nodes

Abstract

In the surgical treatment of breast cancer, the primary tumor is removed together with the sentinel lymph nodes (SLNs). Current clinical procedures involve radioactive compounds (exposing both patient and surgeon) and blue dyes, which often induce long-lasting skin discoloration. Here, we demonstrate the in vivo detection of SLNs in mice using X-ray computed tomography (CT) and near-infrared fluorescence via a dual-modality imaging probe. CT contrast is provided by hafnium oxide nanocrystals, stabilized in physiological buffer using custom designed nitrocatechol ligands. IRDye 800CW is covalently attached to the nanocrystal surface to impart surgery-compatible fluorescence with a high penetration depth. The well-controlled surface functionalization is assessed by 1H NMR spectroscopy, confirming the tight binding of the ligands. During a longitudinal in vivo study the sentinel node is successfully and selectively detected via both imaging modalities 15-30 min postinjection of the probe, allowing for preoperative SLN mapping with X-ray CT and intraoperative removal using fluorescence-guided surgery. Our imaging probe features the correct lymphatic drainage while utilizing fast, economical, and readily available imaging infrastructure, without the need for nuclear medicine or staining molecules.