Functional Imaging to Investigate the Action of Anesthetic on Consciousness
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
The project will involve the development of innovative carbene-based 18F-radiochemistry which will be implemented in the production of commonly used 18F-labeled anesthetic drugs. PET imaging will be used to examine their spatial and temporal biodistribution in vivo, providing valuable insight into the biological mechanisms that cause anesthetics to induce loss of consciousness. The new methods for 18F-radiolabelling that emerge from this project will mainly benefit the scientific community, through a clearer understanding of fluorocarbene reactivity, and radiochemists, by applying these methods to 18F-labeled molecules other than the anesethetics studied. The understanding of the action of anesthetics on consciousness will benefit pharmacologists, clinicians, medical doctors and, indirectly, patients.
People |
ORCID iD |
| Veronique Gouverneur (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M016757/1 | 01/10/2015 | 30/09/2019 | |||
| 1658868 | Studentship | BB/M016757/1 | 01/10/2015 | 30/09/2019 |
| Description | 18F labeling strategies for unmodified peptides with [18F]fluoride require 18F-labeled prosthetics for bioconjugationmore often with cysteine thiols or lysine amines. Here we explore selective radical chemistry to target aromatic residues applying C-H18F-trifluoromethylation. We report a one-step route to [18F]CF3SO2NH4from [18F]fluoride and its application to direct [18F]CF3incorporation at tryptophan or tyrosine residues using unmodified peptides as complex as recombinant human insulin. The fullyautomated radiosynthesis of octreotide[Trp(2-CF218F)] enables in vivo positron emission tomography imaging. |
| Exploitation Route | we have reported the first protocol enabling direct 18F labeling of unmodified peptides at tryptophan andtyrosine residues (with high selectivity for tryptophan) via direct C-H 18F-trifluoromethylation. This method is a new tool to accelerate the discovery of 18F-peptides as imaging agents as well as the development of peptide-based drugs. In view of the number of reactions relying on Langlois-type reagents, [18F]CF3SO2NH4 could expand considerably the radiochemical space for PET applications beyond the peptides described. |
| Sectors | Pharmaceuticals and Medical Biotechnology |