Dataset Information
Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer.
Ontology highlight
ABSTRACT: Background
Surgically induced nerve damage is a common but debilitating side effect in oncological surgery. With the aim to use fluorescence guidance to enable nerve-sparing interventions in future surgery, a fluorescent tracer was developed that specifically targets myelin protein zero (P0).Results
Truncated homotypic P0 protein-based peptide sequences were C-terminally functionalized with the far-red cyanine dye Cy5. The lead compound Cy5-P0101-125 was selected after initial solubility, (photo)physical and in vitro evaluation (including P0-blocking experiments). Cy5-P0101-125 (KD = 105 ± 17 nM) allowed in vitro and ex vivo P0-related staining. Furthermore, Cy5-P0101-125 enabled in vivo fluorescence imaging of the Sciatic nerve in mice after local intravenous (i.v.) administration and showed compatibility with a clinical fluorescence laparoscope during evaluation in a porcine model undergoing robot-assisted surgery. Biodistribution data revealed that i.v. administered [111In]In-DTPA-P0101-125 does not enter the central nervous system (CNS).Conclusion
P0101-125 has proven to be a potent nerve-specific agent that is able to target P0/myelin under in vitro, ex vivo, and in vivo conditions without posing a threat for CNS-related toxicity.
SUBMITTER: Buckle T
PROVIDER: S-EPMC8164657 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer.
EJNMMI research 20210529 1
<h4>Background</h4>Surgically induced nerve damage is a common but debilitating side effect in oncological surgery. With the aim to use fluorescence guidance to enable nerve-sparing interventions in future surgery, a fluorescent tracer was developed that specifically targets myelin protein zero (P0).<h4>Results</h4>Truncated homotypic P0 protein-based peptide sequences were C-terminally functionalized with the far-red cyanine dye Cy5. The lead compound Cy5-P0<sub>101-125</sub> was selected after ...[more]