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 1 H 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.

Remote Control of Energy Transformation‐Based Cancer Imaging and Therapy

“…[ 158 ] With this in mind, a method combining CT imaging and FI for detecting SLNs was proposed. [ 159 ] Specifically, HfO 2 nanocrystals were coupled with NIR fluorescent dye IRDye 800CW to perform dual‐mode imaging of SLNs. As shown in Figure a, after injecting the nanocrystals for 5 min, the contrast enhancement at the SLN could be observed in the CT image, and the signal intensified after 75 and 150 min.…”

“…Reproduced with permission. [ 159 ] Copyright 2023, American Chemical Society. b) Schematic illustration of nano–bio therapeutic emulsion formulated for the synergistic combination of X‐ray photodynamic and anaerobic bacteriolytic therapy.…”

“…Figure 21. a) Coronal slices of CT scans taken at different time points.The SLN area has been highlighted with green, red, and blue rectangles, respectively. Reproduced with permission [159]. Copyright 2023, American Chemical Society.…”

From Gel to Crystal: Mechanism of HfO2 and ZrO2 Nanocrystal Synthesis in Benzyl Alcohol

“…Hafnium oxide nanocrystals are particularly interesting since they are relevant for memory devices, − as X-ray CT contrast agents, − for scintillators, ,, for catalysis, or for radiotherapy . While HfO 2 can be synthesized in benzyl alcohol from HfCl 4 in a pressure bomb (autoclave), the reaction can also be performed in a microwave reactor, considerably shortening the reaction time to 3–4 h .…”

Epitaxial Core/Shell Nanocrystals of (Europium-Doped) zirconia and hafnia

“…1 Colloidal ZrO2 NCs are components for (in)organic composites [2][3][4] while HfO2 NCs find applications in memory devices. 5,6 Due to the high atomic number of hafnium and the high density of hafnia, HfO2 NCs are developed as CT contrast agents, [7][8][9] scintillators, 10 and as radiation therapy enhancers. [11][12][13] Both ZrO2 and HfO2 NCs serve as hosts for optically active lanthanide ions, e.g, europium.…”