1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA;
2. Department of Chemistry, Hunter College and the Graduate Center, City University of New York, New York, NY, USA;
3. Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA;
4. Howard Hughes Medical Institute, New York, NY, USA;
5. Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY, USA;
6. Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA;
7. Department of Radiology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
* These authors contributed equally to this work.
A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright SERRS nanoparticles with a suitable radiotracer would enable pre-operative identification of regions of interest with whole body imaging that can be rapidly corroborated with a Raman imaging device or handheld Raman scanner in order to provide high precision guidance during surgical procedures. Here we present a straightforward new method that produces radiolabeled SERRS nanoparticles for combined positron emission tomography (PET)-SERRS tumor imaging without requiring the attachment of molecular chelators. We demonstrate the utility of these PET-SERRS nanoparticles in several proof-of-concept studies including lymph node (LN) tracking, intraoperative guidance for LN resection, and cancer imaging after intravenous injection. We anticipate that the radiolabeling method presented herein can be applied generally to nanoparticle substrates of various materials by first coating them with a silica shell and then applying the chelator-free protocol.
Keywords: Intrinsic radiolabeling, Surface-enhanced resonance Raman scattering, SERS, Positron emission tomography, in vivo, Imaging.