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

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-P0(101–125) was selected after initial solubility, (photo)physical and in vitro evaluation (including P0-blocking experiments). Cy5-P0(101–125) (K(D) = 105 ± 17 nM) allowed in vitro and ex vivo P0-related staining. Furthermore, Cy5-P0(101–125) 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 [(111)In]In-DTPA-P0(101–125) does not enter the central nervous system (CNS). CONCLUSION: P0(101–125) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00792-9.