New 'Smart' Dual-Modal MR/PET Probes for Zinc Sensing Applications
Lead Research Organisation:
Imperial College London
Department Name: Chemistry
Abstract
Associated with the development of all types of diabetes is the depletion of pancreatic beta-cell mass. It is known that Zn2+ is co-released with insulin from the beta-cells in response to high
glucose levels. Thus, by determination of Zn2+ concentrations in the insulin granules, beta-cell mass can be quantified to understand how its deterioration affects the onset and progression of diabetes. There are however, few imaging probes capable of this function. By the combination of two or more imaging techniques, the limitations associated with each
technique can be synergistically overcome. The project will involve developments towards dual-modal magnetic resonance (MR)/positron imaging tomography (PET) imaging agents that selectively bind to Zn2+ ions within the pancreas, to ultimately achieve a more profound understanding of the role that zinc plays in diabetes.
glucose levels. Thus, by determination of Zn2+ concentrations in the insulin granules, beta-cell mass can be quantified to understand how its deterioration affects the onset and progression of diabetes. There are however, few imaging probes capable of this function. By the combination of two or more imaging techniques, the limitations associated with each
technique can be synergistically overcome. The project will involve developments towards dual-modal magnetic resonance (MR)/positron imaging tomography (PET) imaging agents that selectively bind to Zn2+ ions within the pancreas, to ultimately achieve a more profound understanding of the role that zinc plays in diabetes.
Organisations
People |
ORCID iD |
| Nicholas Long (Primary Supervisor) | |
| Thomas Clough (Student) |
Publications
Clough TJ
(2019)
Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents.
in Nature communications
Clough TJ
(2020)
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of ß-cell-dependent contrast enhancement in the pancreas.
in Dalton transactions (Cambridge, England : 2003)
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509486/1 | 01/10/2016 | 31/03/2022 | |||
| 1955139 | Studentship | EP/N509486/1 | 01/10/2017 | 31/12/2020 | Thomas Clough |
| Description | A novel MRI contrast agent targeted to the insulin-producing cells in the pancreas has been developed. This compound has been tested in vivo using MRI scans to confirm its targeting ability. Additionally, the compound gives a greater signal in tissues with more of these cells, potentially leading towards quantification of their mass. A new family of complexes for luminescence and MRI imaging based on lanthanide chelators also trargeted to these cells has been synthesised and in vitro testing is currently underway. |
| Exploitation Route | The targeted MRI probe acts as a proof of concept that gadolinium-based contrast agents can be targeted to pancreatic islet cells that produce insulin, and this strategy can be developed further to produce other agents. The change in contrast when there is reduced cell mass could lead towards quantification of these cells and potentially act as an early warning system for diabetes development, or could be used to monitor response to any treatment - i.e. a signal increase over time after treatment could suggest a positive response. The targeting group incorporated into the other family of compounds could be utilised to develop new probes to image the pancreas. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |