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

Autor: Buckle T; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. t.buckle@lumc.nl., Hensbergen AW; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands., van Willigen DM; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands., Bosse F; Neurologische Klinik, Heinrich-Heine University Dusseldorf, Düsseldorf, Germany., Bauwens K; ORSI Academy, Melle, Belgium., Pelger RCM; Department of Urology, Leiden University Medical Center, Leiden, The Netherlands., van Leeuwen FWB; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. f.w.b.van_leeuwen@lumc.nl.; ORSI Academy, Melle, Belgium. f.w.b.van_leeuwen@lumc.nl.
Jazyk: angličtina
Zdroj: EJNMMI research [EJNMMI Res] 2021 May 29; Vol. 11 (1), pp. 50. Date of Electronic Publication: 2021 May 29.
DOI: 10.1186/s13550-021-00792-9
Abstrakt: 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.
Databáze: MEDLINE
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