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Developing novel, EphA2 targeted PET molecular imaging technology for glioma 

Lead PI: Dr Simon Puttick, The University of Queensland, QLD

 

 EphA2 imaging

Research idea

PET imaging using radiolabeled antibodies as targeted tracers has the potential to a) provide more specific diagnostic information about tumour infiltration and treatment response compared with current approaches and b) inform on the delivery of antibody-drug conjugates (ADCs) or radioimmunoconjugates as potential therapeutic agents for glioma. In summary, the team’s research platform will target the development of antibodies and single chain variable fragments (scFvs), the binding portion of an antibody, as innovative imaging and possibly theranostic agents for glioma.

Problem

This project aims to tackle three major issues:

  • MRI offers limited information for optimising treatment planning for glioma. In certain cases, PET imaging using non-specific radiotracers can be confounded by local inflammation.
  • There have been no new therapies for glioma since the introduction of temozolamide in 2006. ADCs offer new opportunities for targeted treatment. Innovation lies in the development of radiolabeled ADCs as targeted theranostics.
  • PET imaging is currently limited to sites with access to cyclotron and radiochemistry facilities. This problem can be overcome with appropriate use of labeled EphA2 antibodies or scFvs

Solution

The team will use novel antibodies, scFvs and imaging methods developed in our team to deliver two key objectives:

Develop novel EphA2 antibody or scFv targeted PET imaging agents for glioma that enable full characterization of tumour location and physiology. These new agents will not require direct access to cyclotron facilities.

To use the information provided by these agents to develop efficient targeted antibody-drug conjugates for innovative therapeutic solutions for glioma.

The realisation of these objectives can potentially improve treatment planning and provide an efficient targeted therapeutic for glioma.

"As a young scientist, brain cancer is the final fronier... there are a lot of opportunities for new discoveries, new innovations... that is an exciting opportunity."

- Dr Simon Puttick

Why now?

The assembly of a team with a broad range of experience in medical imaging, cancer biology, biotechnology, chemistry and clinical practice in Brisbane has recently enabled successful completion of a number of important proof of concept studies. The team have access to state-of-the-art preclinical 7T MRI/PET hybrid imaging facilities at the University of Queensland and 3T clinical MRI/PET hybrid imaging facilities at the Herston Imaging Research Facility (RBWH). They are now poised to unlock the full potential of a unique approach to molecular imaging of glioma for advanced treatment planning.

Approach

The proposed project will allow the team to gain a thorough understanding of the potential of EphA2 based PET imaging for glioma management. After completing preclinical studies in animal models outlined in this proposal they aim to move their approach forward to clinical studies. They are ideally positioned to achieve this objective as the assembled team has a strong and broad understanding of disciplines necessary to facilitate clinical translation. In addition, the opening of the Herston Imaging Research Facility, the only imaging facility in Australia with both PET/CT and PET/MRI hybrid imaging technology, will enable translation of their technology. 

Impact

This project has the potential to drive a paradigm shift in the management of glioma. The team aim to deliver a novel diagnostic strategy for glioma that, in addition to providing a unique solution to treatment planning, will inform the rational design of targeted therapies. This innovation could lead to a marked improvement in patient survival rates; successful development of EphA2 conjugates as PET imaging tracers could lead to improved treatment planning, a successful targeted therapy and a personalised medicine approach for glioma. 

Team & Partners

This team has a wide range of expertise and an extensive track record in the successful management of major research projects. Puttick has extensive practical experience in the production and imaging of radiolabelled macromolecules in preclinical investigations. Rose is a recognised expert in the fields of MRI and PET. Whittaker and Thurecht are internationally recognised in preclinical imaging of bioconjugates. Day, Stringer and Boyd are leading experts in the biology of glioma and EphA2. Mahler is an expert in the production and biochemistry of scFvs. Fay is a practicing clinician and expert in neuro-oncology and radiation oncology.

PI:

  • Prof Stephen Rose, The University of Queensland
  • Prof Andrew Boyd, Dr Brett Stringer and Dr Bryan Day, QIMR Berghofer Medical Research Institute
  • Prof Andrew Whittaker, A/Prof Stephen Mahler and Dr Kristofer Thurecht, The University of Queensland
  • Dr Michael Fay, Genesis Cancer Care Newcastle 

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