Imaging Metallomics - Picturing Metal Behaviour in Cancer
Lead Research Organisation:
King's College London
Department Name: Imaging & Biomedical Engineering
Abstract
Metal ions have unique chemical properties that make some of them essential nutrients for human health. On the other hand, if their trafficking is dysregulated this can contribute to development of disease. Many drugs either (i) contain a metal in their structure or (ii) exert their action by influencing metal trafficking in our body.
Drugs based on the metal platinum are widely used in the treatment of several cancers, including ovarian cancer, but unfortunately in many patients the tumour eventually stops responding to treatment and becomes 'platinum resistant', leaving patients with fewer therapeutic options and poorer survival rate.
It has been found, from studies in cells and patient biopsies, that platinum resistant cancer tends to take up less of the platinum drug. While the exact mechanism through which platinum drugs enter the tumours is not fully known, some studies showed that these drugs could use the same 'doorway' into the cell used by copper, a metal essential for our health. Therefore, accumulation of platinum drugs in ovarian cancer, and potentially their ability to respond to these drugs, could be linked to the tumour's ability to accumulate copper.
In this project, I will study the relationship between resistance to platinum drugs in ovarian cancer and its ability to accumulate these drugs and copper. I will also investigate whether removing copper, thus making the tumour more 'hungry' for this essential nutrient, will also trick it into taking up more platinum drugs, potentially reversing platinum resistance.
To study all of this while it's happening inside the body, I will label both the platinum drugs and copper with a radioactive tag so that we can track them inside a living organism in real-time images using a scanner.
This project will not only improve our understanding of why ovarian cancer becomes resistant to platinum drugs but will also enable the development of imaging-based tools to check if a patient's tumour is resistant to platinum drugs, so that the patient can be moved to different treatments. Finally, research into strategies to reverse platinum resistance will help increasing the number of patients that can benefit from platinum drugs.
Drugs based on the metal platinum are widely used in the treatment of several cancers, including ovarian cancer, but unfortunately in many patients the tumour eventually stops responding to treatment and becomes 'platinum resistant', leaving patients with fewer therapeutic options and poorer survival rate.
It has been found, from studies in cells and patient biopsies, that platinum resistant cancer tends to take up less of the platinum drug. While the exact mechanism through which platinum drugs enter the tumours is not fully known, some studies showed that these drugs could use the same 'doorway' into the cell used by copper, a metal essential for our health. Therefore, accumulation of platinum drugs in ovarian cancer, and potentially their ability to respond to these drugs, could be linked to the tumour's ability to accumulate copper.
In this project, I will study the relationship between resistance to platinum drugs in ovarian cancer and its ability to accumulate these drugs and copper. I will also investigate whether removing copper, thus making the tumour more 'hungry' for this essential nutrient, will also trick it into taking up more platinum drugs, potentially reversing platinum resistance.
To study all of this while it's happening inside the body, I will label both the platinum drugs and copper with a radioactive tag so that we can track them inside a living organism in real-time images using a scanner.
This project will not only improve our understanding of why ovarian cancer becomes resistant to platinum drugs but will also enable the development of imaging-based tools to check if a patient's tumour is resistant to platinum drugs, so that the patient can be moved to different treatments. Finally, research into strategies to reverse platinum resistance will help increasing the number of patients that can benefit from platinum drugs.
Organisations
| Description | We performed a seminal study where we looked at distribution of a radioactive version of the endogenous metal copper after it has been administered orally to mice. |
| Exploitation Route | Imaging orally-administered copper is useful not only to give us insights into nutritional pathways of copper in healthy mice (vs cancer models where this may be disrupted) but also because it may lead to use of oral administration (instead of iv) for clinical studies which well lowering regulatory barriers for clinical translation. |
| Sectors | Agriculture Food and Drink Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | While the award has just started it has already generated a lot of interest in different communities that are now looking into using imaging to understand roles of metals in cancer. This is key to the establishment of the new field of Imaging Metallomics in the next couple of years. More interest has also been generated in environmental toxicology to look at the role of metal polluttants using imaging. |
| First Year Of Impact | 2025 |
| Sector | Chemicals,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Clinical production of manganese-52 for mechanistic studies in humans using Total-Body PET |
| Amount | £79,189 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2024 |
| End | 03/2026 |
| Description | King's-Cornell Global Strategic Collaboration Awards |
| Amount | £8,000 (GBP) |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2025 |
| End | 12/2025 |
| Description | Radionuclide imaging to study the immunological effects of copper depletion in high-risk neuroblastoma |
| Amount | £25,000 (GBP) |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2024 |
| End | 10/2024 |
| Description | Imaging copper depletion in breast cancer models |
| Organisation | Cornell University |
| Department | Weill Cornell Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have just recently started this collaboration helped by a King's-Cornell Global Strategic Collaboration Awards ($5000 + £4000) that will allow my PDRA to undertake a visit in Dr Vivek Mittal's lab to familiarise with a specific triple negative breast cancer model and technique which we can then replicate at KCL. Our contributions will be on imaging copper and other metals at a tissue and whole body level using Laser Ablation Inductively Coupled Mass Spectrometry and Positron Emission Tomography, respectively, |
| Collaborator Contribution | They will provide us with the mouse models as well as traditional cancer research expertise. |
| Impact | As the collaboration just started no results have been obtained yet |
| Start Year | 2025 |
| Description | Imaging the immunological effects of copper depletion in high-risk neuroblastoma |
| Organisation | Queen Mary University of London |
| Department | Barts Cancer Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We recently started this collaboration supported by a CRUK Development fund to image the effect of copper depletion in mouse models of neuroblastoma. My group provide imagung expertise, in addition to metals in medicine expertise. |
| Collaborator Contribution | Collaborators will provide expertise in the target receptor, radiolabelled antibody as well as translational pathways for impact. |
| Impact | As the collaboration has just started no outcomes are available yet |
| Start Year | 2024 |
| Description | Imaging the immunological effects of copper depletion in high-risk neuroblastoma |
| Organisation | University College Hospital |
| Department | University College London Hospitals Charity (UCLH) |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | We recently started this collaboration supported by a CRUK Development fund to image the effect of copper depletion in mouse models of neuroblastoma. My group provide imagung expertise, in addition to metals in medicine expertise. |
| Collaborator Contribution | Collaborators will provide expertise in the target receptor, radiolabelled antibody as well as translational pathways for impact. |
| Impact | As the collaboration has just started no outcomes are available yet |
| Start Year | 2024 |
