Figure 2.
Imaging of cancer with microscopic precision using a new generation of Raman nanoparticles. (A) SERRS-nanostars. Left: Diagram, 3D rendering and electron microscopy images. SERRS-nanostars consist of a star-shaped gold core surrounded by a near-infrared Raman reporter and a silica shell that is produced without the use of surface primers. Right: phantom with decreasing concentrations of SERRS-nanostars, acquired using in vivo imaging settings. The detection threshold is approximately 1.5 femtomolar (fM). (B, C) After intravenous injection of only 30 fmol/g, SERRS-nanostars enable visualization of microscopic infiltration at tumor margins and regional satellite metastases. Experiments were performed in a human dedifferentiated liposarcoma mouse model. SERRS images were acquired 16–18 h after injection, and signal intensity is displayed in counts/s. (B) Imaging of residual cancer in the resection bed. A SERRS image (left) of the resection bed was acquired after surgical excision of the bulk tumor. The resection was guided by white light only, with the surgeon being blinded to the SERRS images. Immunohistochemistry (IHC) correlation (middle, right) confirmed that the SERRS positive signal (arrows 1 and 2) represented microscopic residual cancer at the margins of the resection bed. IHC images on the far right are magnified views of the areas indicated with arrows 1 and 2. (C) Imaging of regional satellite micrometastases. In a different mouse bearing a liposarcoma, a SERRS image (left) was acquired approximately 1 cm adjacent to the visible margin of the tumor. Note multiple small foci of Raman signal (arrows 1 to 5). As confirmed by IHC (middle, right), each of these five foci correlated with a separate tumor cell cluster (vimentin+) as small as 100 µm (micrometastases). Images on far right are magnified views of the metastases labeled 4 and 5. Adapted, with permission, from reference (10).