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

EJNMMI Research, vol. 11, pp. 50

Abstract

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.

Authors 7

1. Tessa Buckle corresponding Aachen Interventional Molecular Imaging Laboratory Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. t.buckle@lumc.nl

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

2. Albertus Wijnand Hensbergen Aachen Interventional Molecular Imaging Laboratory Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

3. Danny M. van Willigen Aachen Interventional Molecular Imaging Laboratory Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

4. Frank Bosse

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Neurologische Klinik, Heinrich-Heine University Dusseldorf, Düsseldorf, Germany

5. Kevin P. Bauwens

   ORSI Academy

   Affiliation as printed

   ORSI Academy, Melle, Belgium

6. Rob C.M. Pelger Aachen Department of Urology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Urology, Leiden University Medical Center, Leiden, The Netherlands

7. Fijs W. B. van Leeuwen corresponding Aachen Interventional Molecular Imaging Laboratory Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center · ORSI Academy

   Affiliation as printed

   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

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

   ORSI Academy, Melle, Belgium