4.1 Article

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

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CHURCHILL LIVINGSTONE
DOI: 10.1016/j.bjoms.2018.11.003

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Head and neck squamous cell carcinoma; Intraoperative margin control; Cytology; RGD peptide; Fluorescence imaging; Integrins; alpha v beta 6 integrin

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We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin alpha v beta 6 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 alpha v beta 6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin alpha v beta 6-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 alpha v beta 6 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 alpha v beta 6-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. i3/4(C) 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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