Poster Presentation 8th Venoms to Drugs 2023

Development and validation of nerve-targeted bacteriochlorin sensors (#105)

Javier Hernández-Gil 1 2 3 , Chun Yuen Chow 4 5 , Hugo Chatras 6 , Paula Demétrio de Souza França 1 7 , Zachary V Samuels 1 , Mike Cornejo 1 , Glenn F King 4 5 , Jason S Lewis 1 8 9 10 , Thomas Reiner 1 8 9 10 , Junior Gonzales 1 6 11
  1. Department of Radiology, Memorial Sloan Kettering Cancer Centre, New York, USA
  2. Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Herestraat, Leuven, Belgium
  3. Instituto de Tecnología Química, Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Valencia, Spain
  4. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  5. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD, Australia
  6. Department of Chemistry, Cleveland State University, Cleveland, Ohio, USA
  7. Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paulo, São Paulo, Brazil
  8. Department of Pharmacology, Weill-Cornell Medical College, New York, USA
  9. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Centre, New York, USA
  10. Department of Radiology, Weill Cornell Medical College, New York, USA
  11. Centre for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, Ohio, USA

During oncological surgery or after traumatic injury, surgeons often face difficulties in precisely locating and preserving vital nerve structures due to tissue distortion and poor visibility. This can lead to unintended nerve injuries that impose significant physical, psychological, and economic burden on individuals and their families. Thus, intraoperative visualisation of nerves is an unmet clinical need. The voltage-gated sodium channel NaV1.7 is expressed on most peripheral nerves and therefore it represents an ideal target for imaging purposes. Hs1a is a potent peptidic inhibitor of NaV1.7 isolated from the venom of the Chinese tarantula Cyriopagopus schmidti. Here we report the labelling of Hs1a with a bacteriochlorin fluorophore (Hs1a-Bac). Intravenous injection of Hs1a-Bac leads to high uptake in the peripheral nerves of mice. Biodistribution studies revealed that Hs1a-Bac accumulates in spleen, liver, and kidney, but not other organs such as muscles, heart, and brain. Radiolabelling Hs1a-Bac with 64Cu provides a strategy for rapid assessment of nerve damage and intraoperative surgical intervention by using positron emission tomography/computed tomography (PET-CT) and Cerenkov luminescence (CL) imaging, respectively. 64Cu-labelled Hs1a-Bac produced adequate fluorescent signals in the brachial plexus and sciatic nerves in whole-body CL images. Our results demonstrate the feasibility of using a NaV1.7-targeted venom peptide as a multimodal imaging agent and validate the neural specificity and fluorescent imaging properties of 64Cu-labelled Hs1a-Bac. In addition to providing a starting point for intraoperative nerve visualisation, Hs1a offers valuable insights into the complex anatomy and function of the peripheral nervous system. Clinical translation of this imaging agent would minimise nerve damage during surgery, thereby reducing surgical morbidity.