Optical SmartProbe development for Molecular Imaging of the Ex Vivo Perfused Human Lung
Lead Research Organisation:
University of Edinburgh
Department Name: MRC Centre for Inflammation Research
Abstract
The prospect of an optical biopsy to interrogate the human lungs offers to improve the robustness of clinical trials, drug discovery programmes, while also outcomes for critically ill patients. Optical molecular imaging using smart fluorescent probes offers a safe and affordable technique that will allow analysis of multiple lung pathologies and diseases. Given the lack of current viable chemical probes for the diagnostics of chronic conditions affecting the lungs, the aim of this project is to synthesise several SmartProbes and validate their biological utility. With these probes we will investigate the function of alternatively activated macrophages and the epithelium.
Publications
Cherukaraveedu D
(2019)
Solid-phase synthesis of biocompatible N-heterocyclic carbene-Pd catalysts using a sub-monomer approach.
in Organic & biomolecular chemistry
Birch GP
(2019)
Optical Molecular Imaging of Inflammatory Cells in Interventional Medicine-An Emerging Strategy.
in Frontiers in oncology
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/N503940/1 | 01/10/2015 | 30/09/2019 | |||
| 1732641 | Studentship | BB/N503940/1 | 14/09/2015 | 31/08/2019 | Gavin Birch |
| Description | Macrophages are a valuable imaging target due to their key role in maintaining homeostasis and responding to inflammatory stimuli in the lung. Imaging these cells will allow us to dynamically observe macrophage biology and the multitude of host cell interactions within the lung. SmartProbes were targeted to macrophages via the cell specific markers - the macrophage mannose and folate receptors. The synthesis of SmartProbes targeting the folate receptor, including the application of new solid phase methodology to simplify the synthesis of these probes, is reported. In vitro studies were carried out in cancer cells and primary human monocyte-derived macrophages. An anti-MMR nanobody that targets the mannose receptor was fluorescently labelled to give a near-infrared SmartProbe. Its specificity and selectivity was assessed with primary immune cells and ex vivo clinical lung samples. |
| Exploitation Route | To advance this research, in vivo validation of the biocompatibility and toxicology of each probe is required. |
| Sectors | Pharmaceuticals and Medical Biotechnology |