ABSTRACT
We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin αvß6 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 αvß6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin αvß6-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 αvß6 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 αvß6-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.
Subject(s)
Antigens, Neoplasm , Carcinoma, Squamous Cell/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Integrins , Oligopeptides , Optical Imaging/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnosis , Cell Line, Tumor , Female , Head and Neck Neoplasms/diagnosis , Humans , Male , Middle AgedABSTRACT
Cell-penetrating peptides (CPPs) present a versatile alternative to viral gene delivery vectors, addressing the still challenging task to suitably transport the desired gene to the target cell. In this work, the rational design of triazole-bridged CPPs and their detailed investigation concerning peptide/lipid interactions, using also NMR-based structure calculations, are reported.