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EJNMMI Research
Published in: EJNMMI Research 1/2021

Open Access 01-12-2021 | Original research

Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer

Authors: Tessa Buckle, Albertus. W. Hensbergen, Danny M. van Willigen, Frank Bosse, Kevin Bauwens, Rob C. M. Pelger, Fijs W. B. van Leeuwen

Published in: EJNMMI Research | Issue 1/2021

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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.
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Metadata
Title
Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer
Authors
Tessa Buckle
Albertus. W. Hensbergen
Danny M. van Willigen
Frank Bosse
Kevin Bauwens
Rob C. M. Pelger
Fijs W. B. van Leeuwen
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2021
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-021-00792-9

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