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

Buckle, T.; Hensbergen, A.W.; Willigen, D.M. van; Bosse, F.; Bauwens, K.; Pelger, R.C.M.; Leeuwen, F.W.B. van

doi:doi:10.1186/s13550-021-00792-9

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 [In...Show moreBackground 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 [In-111]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.Show less

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