Current identification of nerves during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, relationship to surrounding structures to distinguish nerves from non-nerve tissues. In instances of trauma, tumor invasion or infection, nerve identification using the above criteria may be challenging. We have identified a peptide sequence, Nerve Peptide 41 (NP41) through phage display that preferentially binds to peripheral nerves compared to adjacent non-nerve tissue after systemic administration. Systemic injection of this peptide into rodents results in specific nerve labeling beginning at 2 hours. Useful nerve-specific fluorescence lasts up to 8 hours following a single intravenous injection, allowing more accurate identification of small and buried nerve branches when compared to visualization with white light reflectance alone. In this study, we propose to accomplish the following specific aims: 1) Show proof of concept in using NP41 for surgical molecular guidance in animal models and in excised human nerves of the head and neck, 2) Show proof of concept in using nerve peptides for to label the autonomic nerves coursing along the prostate gland in animal models and in excised human specimens, 3) Optimize NP41 in preparation for preclinical testing A nerve specific fluorescent label has the potential to provide surgeons with a molecular marker visualizable in real time to distinguish nerve from non-nerve tissue, thereby improving surgical accuracy and avoid inadvertent injury. Together, the above studies will yield several proof of concept studies in animal models of head and neck surgery and prostate surgery to test the surgical outcome using fluorescence labeling of nerves with the aim toward eventual use of NP41 during head and neck surgery and nerve-sparing radical prostatectomy in patients.

Public Health Relevance

Current identification of nerves during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, relationship to surrounding structures to distinguish nerves from non-nerve tissues. We have identified a peptide sequence, Nerve Peptide 41 (NP41) through phage display that preferentially binds to peripheral nerves compared to adjacent non-nerve tissue after systemic administration.
The aim of this study is to develop several proof of concept studies in animal models of head and neck surgery and prostate surgery to test the surgical outcome using fluorescence labeling of nerves with the aim toward eventual use of NP41 during head and neck surgery and nerve-sparing radical prostatectomy in patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB014929-01A1
Application #
8399499
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Krosnick, Steven
Project Start
2012-08-08
Project End
2016-07-31
Budget Start
2012-08-08
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$348,750
Indirect Cost
$123,750
Name
University of California San Diego
Department
Surgery
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hussain, Timon; Nguyen, Linda T; Whitney, Michael et al. (2016) Improved facial nerve identification during parotidectomy with fluorescently labeled peptide. Laryngoscope 126:2711-2717
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Hussain, Timon; Savariar, Elamprakash N; Diaz-Perez, Julio A et al. (2016) Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers. Head Neck 38:715-23
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Hauff, Samantha J; Raju, Sharat C; Orosco, Ryan K et al. (2014) Matrix-metalloproteinases in head and neck carcinoma-cancer genome atlas analysis and fluorescence imaging in mice. Otolaryngol Head Neck Surg 151:612-8
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