High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model

Fabio Feroldi*, Mariska Verlaan, Helene Knaus, Valentina Davidoiu, Danielle J. Vugts, Guus A.M.S. Van Dongen, Carla F.M. Molthoff, Johannes F. De Boer

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Abstract

With the emergence of immunotherapies for cancer treatment, there is a rising clinical need to visualize the tumor microenvironment (TME) non-invasively in detail, which could be crucial to predict the efficacy of therapy. Nuclear imaging techniques enable whole-body imaging but lack the required spatial resolution. Conversely, near-infrared immunofluorescence (immuno-NIRF) is able to reveal tumor cells and/or other cell subsets in the TME by targeting the expression of a specific membrane receptor with fluorescently labeled monoclonal antibodies (mAb). Optical coherence tomography (OCT) provides three-dimensional morphological imaging of tissues without exogenous contrast agents. The combination of the two allows molecular and structural contrast at a resolution of ~15 µm, allowing for the specific location of a cell-type target with immuno-NIRF as well as revealing the three-dimensional architectural context with OCT. For the first time, combined immuno-NIRF and OCT of a tumor is demonstrated in situ in a xenograft mouse model of human colorectal cancer, targeted by a clinically-safe fluorescent mAb, revealing unprecedented details of the TME. A handheld scanner for ex vivo examination and an endoscope designed for imaging bronchioles in vivo are presented. This technique promises to complement nuclear imaging for diagnosing cancer invasiveness, precisely determining tumor margins, and studying the biodistribution of newly developed antibodies in high detail.

Original languageEnglish
Article number#346860
Pages (from-to)6186-6204
Number of pages19
JournalBiomedical Optics Express
Volume9
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Image quality
  • Imaging techniques
  • Magnetic resonance imaging
  • Optical imaging
  • Real time imaging
  • Three dimensional imaging

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