A Truncated 14-Amino-Acid Myelin Protein-Zero-Targeting Peptide for Fluorescence-Guided Nerve-Preserving Surgery

Abstract

Background: The occurrence of accidental nerve damage during surgery and the increasing application of image guidance during head-and-neck surgery have highlighted the need for molecular targeted nerve-sparing interventions. The implementation of such interventions relies on the availability of nerve-specific tracers. In this paper, we describe the development of a truncated peptide that has an optimized affinity for protein zero (P0), the most abundant protein in myelin. Methods and Materials: Further C- and N-terminal truncation was performed on the lead peptide Cy5-P0101–125. The resulting nine Cy5-labelled peptides were characterized based on their photophysical properties, P0 affinity, and in vitro staining. These characterizations were combined with evaluation of the crystal structure of P0, which resulted in the selection of the optimized tracer Cy5-P0112–125. A near-infrared Cy7-functionalized derivative (Cy7-P0112–125) was used to perform an initial evaluation of fluorescence-guided surgery in a porcine model. Results: Methodological truncation of the 26-amino-acid lead compound Cy5-P0101–125 resulted in a size reduction of 53.8% for the optimized peptide Cy5-P0112–125. The peptide design and the 1.5-fold affinity gain obtained after truncation could be linked to interactions observed in the crystal structure of the extracellular portion of P0. The near-infrared analogue Cy7-P0112–125 supported nerve illumination during fluorescence-guided surgery in the head-and-neck region in a porcine model. Conclusions: Methodological truncation yielded a second-generation P0-specific peptide. Initial surgical evaluation suggests that the peptide can support molecular targeted nerve imaging.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013–2023)

“…Published in Ca-A Cancer Journal for Clinicians (IF=254.7, Q1) in 2022, one review written by Pomper Martin G. comprehensively supported the current application and clinical value of molecular imaging technique, pointing a promising future direction of IGS 39 . The latest researches of van Leeuwen Fijs W. B. had focused on the application of robotic surgery and fluorescence guidance in the treatment of PCa 40 – 44 . Two clinical researches 42 , 43 expressed the optimistic prospective of fluorescence imaging-guided robot-assisted laparoscopic prostatectomy.…”