State-of-the-Art Equipment for Preclinical Molecular Imaging and Targeted Radiotherapy

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

Numerous chronic diseases, such as cancer and early heart disease, are often symptomless. Consequently, these diseases are often diagnosed at a late stage which reduces the treatment options that are available to the patient. We are creating new ways of seeing inside the body to identify the processes that go wrong with these devastating diseases using a process called 'molecular imaging'. These innovative scans require the administration of radioactive drugs into the blood stream. The drugs home to the site of the disease, or identify a particular feature related to the disease that will help medical professionals provide the correct treatments for the specific patient. The radioactivity is needed so advanced medical scanners can identify the disease location in the body. Instead of taking a picture of the outside, these scanners can see deep within the body and locate regions of disease that are just millimetres in size. The type and amount of radioactivity used are not harmful but provide the 'beacon' so these diseases can visualised by the scanner.

At King's College London we have pioneered the discovery of new molecular imaging applications for the past fifteen+ years. We have built a critical mass and extensive research infrastructure to make pioneering discoveries in molecular imaging research with the ultimate goal of improving human health. This exciting area of research is now on the cusp of new discoveries to not only see but treat disease. By changing the nature of the radioactivity attached to the drug we can deliver a targeted therapeutic payload to the site of disease, resulting in its elimination. Known as 'radionuclides therapies', they have already shown improvements over normal chemotherapy in prostate cancer patients with a lower number of side effects. At King's College London we have the facilities, know-how and ambition to make a significant contribution to this emerging field of research.

To fully exploit our critical mass in molecular imaging and radionuclide research we require new scanners to detect both imaging and therapeutic radioactivity. Here, we have requested funds to purchase miniaturised clinical scanners for research using animal models of human diseases. Replacing our >12-year-old equipment they possess advanced features that enable researchers to develop and optimise these imaging tools before their use in humans. Specifically, we will be able to track the movement of these radioactivity-based treatments throughout the body in real time. The improved resolution of the scans will also allow us to identify microstructures in the body or track just a few thousand therapeutic cells that are injected to fight cancer. Working with researchers across the UK will use these scanners to improve our understanding of a host of different diseases including cancer, neurodegenerative disorders, heart disease, pregnancy, inflammatory disorders, and arthritis. Finally, by partnering with pharmaceutical and biotech companies we aim to commercialise these discoveries to deliver maximum benefit to a wide range of patients both in the UK and world-wide.

Technical Summary

King's College London (KCL) has the UK's largest concentration of academics dedicated to molecular imaging research and development. Our established preclinical imaging research facility has successfully operated since 2009 using a cost recovery model, with supporting infrastructure, scientific and key technical expertise embedded within KCL. Through this proposal we will significantly enhance our programme of preclinical imaging research through the creation of a state-of-the-art theranostics equipment platform. Specifically, we will replace our aging (>12 years) and no long fit-for-purpose preclinical PET/CT and SPECT/CT scanners with next-generation systems equipped with new high-sensitivity detectors with large axial fields of view. These scanners will provide significant new capabilities, including simultaneous multi-animal and multi-tracer imaging at sub-mm resolution, AI integration for enhanced image segmentation/processing, advanced kinetic modelling to improve reliability and accuracy of image quantitation, and importantly, spatiotemporal quantitation of both diagnostic and therapeutic radionuclides. Leveraging our strengths in biology, chemistry, engineering, AI and clinical translation, these scanners will allow state-of the-art developments in preclinical molecular imaging and underpin game-changing clinical nuclear medicine applications total body PET and theranostics. Supporting MRC key strategic priorities, we will (i) image disease processes faster and more accurately, at an earlier stage, and with greater resolution (precision health); (ii) develop new strategies incorporating targeted radiotherapy to treat disseminated cancer (advanced therapies); and (iii) enhance our understanding of disease biology.

Publications

10 25 50
 
Description What were the most significant achievements from the award?
Development of new imaging methods to assess disease in living animals.

To what extent were the award objectives met? If you can, briefly explain why any key objectives were not met.
Successful installation of new imaging scanners, facility refurbishment, and collaborations initiated.

How might the findings be taken forward and by whom?
The imaging platform will run for the next decade, supporting imaging research at King's, the development of new diagnostic tools, and the training of the next-generation of imaging scientists.
Exploitation Route We are currently developing a model by which users outside of King's, and commercial entities can gain access to our system, providing added value for the imaging community.
Sectors Education

Healthcare

Pharmaceuticals and Medical Biotechnology

 
Title AI tool to assess therapy resistance 
Description AI/deep learning method to identify therapy resistant cancer from PET imaging scans. 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact None yet as still in development. 
 
Title Imaging agent to detect therapy resistant cancer - FSPG 
Description Development of a novel positron emission tomography agents that binds to the amino acid transporter, xCT. Results in the identification of therapy resistant cancer in living subjects. 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? Yes  
Impact Clinical trial initiated (NCT05889312) funded by RoseTrees and GST Charity. Adoption of imaging methods by others. 
 
Title NanoMIP for xCT 
Description Specific nanoparticle for the binding and treatment of therapy-resistant cancer 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact N/A as still in development. 
 
Description AI assessment of therapy resistant cancer 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Creation of a new imaging agent to detect therapy resistant cancer. Imaging across eight different tumour types to provide extensive dataset for AI assessment.
Collaborator Contribution AI model creation and evaluation of our imaging dataset.
Impact Multidisciplinary research: Incorporates tumour biology, imaging research, and deep learning/mathematical modelling. Outputs are pending.
Start Year 2024
 
Description Cancer metabolomics 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Determination of the molecular mechanisms that drive changes in the uptake of our radiotracer, FSPG
Collaborator Contribution Processing and interpretation of isotope-tracing metabolomics
Impact Multidisciplinary (medical imaging, biology, metabolomics) Outputs: P.N. McCormick, H.E. Greenwood, M. Glaser, O.D.K. Maddocks, T. Gendron, K. Sander, G. Gowrishankar, A. Hoehne, T. Zhang, A.J. Shuhendler, D.Y. Lewis, M. Berndt, N. Koglin, M.F. Lythgoe, S.S. Gambhir, E. Årstad and T.H. Witney (2019). Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity. Cancer Res 79, pp.853-863. H.E. Greenwood, P.N. McCormick, T. Gendron, M. Glaser, R. Pereira, O.D.K Maddocks, K. Sander, T. Zhang, N. Koglin, M.F. Lythgoe, E. Årstad, D. Hochhauser and T.H. Witney (2019). Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clin Cancer Res 25, pp.2471-2482.
Start Year 2017
 
Description Creation of nanoMIPs targeting therapy resistant cancer 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Generate know-how regarding lung cancer biology, tumour models, and therapeutic targets. Evaluate the resulting therapeutics.
Collaborator Contribution Development of a novel nanoMIP that targets a biomarker, xCT, expressed in therapy-resistant tumours.
Impact Multidisciplinary research: incorporating cancer biology, imaging research, medicinal and polymer chemistry.
Start Year 2023
 
Description Evaluation of glutamate metabolism in cancer 
Organisation Life Molecular Imaging
Country Germany 
Sector Private 
PI Contribution Biological evaluation of the radiotracer FSPG as a sensitive readout of tumour redox status and the use of this non-invasive imaging technique to predict tumour resistance to therapy.
Collaborator Contribution FSPG radiosynthesis optimisation, provision of FSPG clinical-grade precursor and research funding
Impact Multidisciplinary (chemistry, radiochemistry, biology, medical imaging) Outputs: P.N. McCormick, H.E. Greenwood, M. Glaser, O.D.K. Maddocks, T. Gendron, K. Sander, G. Gowrishankar, A. Hoehne, T. Zhang, A.J. Shuhendler, D.Y. Lewis, M. Berndt, N. Koglin, M.F. Lythgoe, S.S. Gambhir, E. Årstad and T.H. Witney (2019). Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity. Cancer Res 79, pp.853-863. H.E. Greenwood, P.N. McCormick, T. Gendron, M. Glaser, R. Pereira, O.D.K Maddocks, K. Sander, T. Zhang, N. Koglin, M.F. Lythgoe, E. Årstad, D. Hochhauser and T.H. Witney (2019). Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clin Cancer Res 25, pp.2471-2482.
Start Year 2014
 
Description Imaging immune-mediated ferroptosis 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution This collaboration between GSK and the CRUK City of London Centre seeks to use the novel PET radiotracers developed during this SHD Fellowship to assess an iron-dependent form of cell death, named ferroptosis, in a range of solid tumours. We are in the process of mechanistically validating our radiotracers as response markers both in cells and in animal models of cancer. Once validated, this imaging agent will be used to monitor response to immune-modulating checkpoint inhibitors with an aim to differentiate responders from non-responders.
Collaborator Contribution GSK - provision of consumables to fund the project CRUK - sponsorship of 1x FTE PDRA for 3 years
Impact Multidisciplinary (chemistry, biology, medical imaging) Outputs: GSK project funding
Start Year 2020
 
Description Interactive talk and workshop "Radioactivity - the overlooked cancer remedy" at the Thriving Minds symposium, Sancton Wood School, Cambridge, hosted by Lucy Hawking. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact 80 pupils from across the country attended our interactive 2h workshop on the medical uses of radioactivity. The pupils gained a new understanding of the benefits, not just the risks of radiation, it's use in everyday life, and how it can be used to treat cancer patients. There was a lively discussion in this interactive workshop, which included practical activities, such as locating where the radioactive substance was inside a representation of a human body. The event was covered by the Cambridge local press and we got very positive feedback from the teachers, students, and organiser Lucy Hawking (Stephen Hawking's daughter).
Year(s) Of Engagement Activity 2023