uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model

Oncotarget. 2017 Feb 28;8(9):15407-15419. doi: 10.18632/oncotarget.14282.


Purpose: Urokinase-like Plasminogen Activator Receptor (uPAR) is overexpressed in a variety of carcinoma types, and therefore represents an attractive imaging target. The aim of this study was to assess the feasibility of two uPAR-targeted probes for PET and fluorescence tumor imaging in a human xenograft tongue cancer model.

Experimental design and results: Tumor growth of tongue cancer was monitored by bioluminescence imaging (BLI) and MRI. Either ICG-Glu-Glu-AE105 (fluorescent agent) or 64Cu-DOTA-AE105 (PET agent) was injected systemically, and fluorescence imaging or PET/CT imaging was performed. Tissue was collected for micro-fluorescence imaging and histology. A clear fluorescent signal was detected in the primary tumor with a mean in vivo tumor-to-background ratio of 2.5. Real-time fluorescence-guided tumor resection was possible, and sub-millimeter tumor deposits could be localized. Histological analysis showed co-localization of the fluorescent signal, uPAR expression and tumor deposits. In addition, the feasibility of uPAR-guided robotic cancer surgery was demonstrated. Also, uPAR-PET imaging showed a clear and localized signal in the tongue tumors.

Conclusions: This study demonstrated the feasibility of combining two uPAR-targeted probes in a preclinical head and neck cancer model. The PET modality provided preoperative non-invasive tumor imaging and the optical modality allowed for real-time fluorescence-guided tumor detection and resection. Clinical translation of this platform seems promising.

Keywords: PET; head and neck cancer; image-guided surgery; tumor margin assessment; uPAR.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / surgery
  • Cell Line, Tumor
  • Feasibility Studies
  • Female
  • Fluorescent Dyes / chemistry
  • Head and Neck Neoplasms / diagnostic imaging
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / surgery*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Mice, Inbred Strains
  • Mice, Nude
  • Optical Imaging / methods
  • Positron Emission Tomography Computed Tomography / methods*
  • Receptors, Urokinase Plasminogen Activator / analysis*
  • Reproducibility of Results
  • Spectroscopy, Near-Infrared / methods*
  • Surgery, Computer-Assisted / methods*
  • Tongue Neoplasms / diagnostic imaging
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / surgery
  • Xenograft Model Antitumor Assays*


  • Fluorescent Dyes
  • Receptors, Urokinase Plasminogen Activator