Fluorescence imaging of invasive head and neck carcinoma cells with integrin αvβ6-targeting RGD-peptides: an approach to a fluorescence-assisted intraoperative cytological assessment of bony resection margins

Br J Oral Maxillofac Surg. 2018 Dec;56(10):972-978. doi: 10.1016/j.bjoms.2018.11.003. Epub 2018 Nov 28.


We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin αvβ6 as a potential approach for a fluorescence-assisted intraoperative cytological assessment of bony resection margins (F-AICAB) in patients who had bone-infiltrating squamous cell carcinoma (SCC) of the head and neck. This was assessed to demarcate invasive carcinoma cells that stained for αvβ6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin αvβ6-targeting fluorescence-labelled RGD peptides were added to the cytological samples and the accuracy of the resulting signal assessed by comparing it with the cytological findings. The value of F-AICAB was evaluated to find out if it could help to improve future diagnoses, tests, and treatments. Integrin αvβ6 was strongly expressed in invasive SCC cells and qualified as a marker for bone-infiltrating carcinoma cells. It showed a high affinity to bind to invasive SCC cells and enabled swift and specific demarcation of αvβ6-stained carcinoma cells. It was also diagnostic, with a sensitivity of 100% (95% CI 81.3% to 99.3%), specificity of 98.3% (95% CI 94.4% to 99.0%), positive predictive value of 92% (95% CI 70.2% to 94.3%), and negative predictive value of 100% (95% CI 96.9% to 99.9%), compared with the cytological findings. The targeting of specific integrin subtypes with selective, synthetic ligands, adapted for multimodal imaging, is a promising new approach to diagnosis. Further studies are necessary to provide more evidence for successful clinical translation and to establish the impact on clinical procedures.

Keywords: Cytology; Fluorescence imaging; Head and neck squamous cell carcinoma; Integrins; Intraoperative margin control; RGD peptide; αvβ6 integrin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Cell Line, Tumor
  • Female
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / diagnostic imaging*
  • Humans
  • Integrins*
  • Male
  • Middle Aged
  • Oligopeptides*
  • Optical Imaging / methods*


  • Antigens, Neoplasm
  • Integrins
  • Oligopeptides
  • integrin alphavbeta6
  • arginyl-glycyl-aspartic acid