Targeted multicolor in vivo imaging over 1,000 nm enabled by nonamethine cyanines

Venu G Bandi1, Michael P Luciano1, Mara Saccomano2, Nimit L Patel3, Thomas S Bischof2, Jakob G P Lingg2, Peter T Tsrunchev2, Meredith N Nix1, Bastian Ruehle4, Chelsea Sanders5, Lisa Riffle3, Christina M Robinson5, Simone Difilippantonio5, Joseph D Kalen3, Ute Resch-Genger4, Joseph Ivanic6, Oliver T Bruns7,8,9,10, Martin J Schnermann11

  1. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  2. Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.
  3. Small Animal Imaging Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
  4. Biophotonics Division, Federal Institute of Materials Research and Testing, BAM, Berlin, Germany.
  5. Animal Research Technical Support, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
  6. Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
  7. Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany. oliver.bruns@helmholtz-muenchen.de.
  8. Department of Medicine, Technische Universität München, Munich, Germany. oliver.bruns@helmholtz-muenchen.de.
  9. Division of Functional Imaging in Surgical Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany. oliver.bruns@helmholtz-muenchen.de.
  10. Carl Gustav Carus Faculty of Medicine, TU Dresden, Dresden, Germany. oliver.bruns@helmholtz-muenchen.de.
  11. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. martin.schnermann@nih.gov.

Abstract

Recent progress has shown that using wavelengths between 1,000 and 2,000 nm, referred to as the shortwave-infrared or near-infrared (NIR)-II range, can enable high-resolution in vivo imaging at depths not possible with conventional optical wavelengths. However, few bioconjugatable probes of the type that have proven invaluable for multiplexed imaging in the visible and NIR range are available for imaging these wavelengths. Using rational design, we have generated persulfonated indocyanine dyes with absorbance maxima at 872 and 1,072 nm through catechol-ring and aryl-ring fusion, respectively, onto the nonamethine scaffold. Multiplexed two-color and three-color in vivo imaging using monoclonal antibody and dextran conjugates in several tumor models illustrate the benefits of concurrent labeling of the tumor and healthy surrounding tissue and lymphatics. These efforts are enabled by complementary advances in a custom-built NIR/shortwave-infrared imaging setup and software package for multicolor real-time imaging.

Presented By Mara Saccomano | ORCID iD