Early-stage clinical development of a PET imaging agent for future commercialisation

Prof Andy Sutherland and Dr Adriana Tavares in front of a patient scanner at QMRI, Edinburgh

Professor Andrew Sutherland and the Sutherland group, in collaboration with the Tavares Group at the University of Edinburgh, have successfully developed a revolutionary new radiotracer that will enable the use of Positron Emission Tomography (PET) scans to diagnose a range of inflammation-associated diseases, including Alzheimer’s and Parkinson’s, as well as myocardial infarction. Two IAA projects supported the clinical development and commercialisation of the new tracer agent, LW223.

The challenge

PET scans produce high-resolution, three-dimensional images of the body. The patient is injected with a non-toxic radiotracer, designed to selectively bind to biological receptors associated with a particular disease, resulting in an accurate diagnosis and prognosis. PET scans are routinely used for the diagnosis of cancer.

For the diagnostic potential of PET scans to be broadened to other diseases, new tracer agents need to be developed that will bind targets specific to those conditions. Scientists know that increased levels of the translocator protein (TSPO) in cells occur in many inflammatory disorders, and particularly in neuroinflammatory and cardiovascular conditions such as Alzheimer’s and Parkinson’s disease, and in cardiovascular and brain tissue after a stroke. TSPO is therefore of great interest as a target protein in the diagnosis and treatment of such diseases associated with inflammation.

Response

Over a ten-year period, the Sutherland Group at the University of Glasgow and the Tavares Group at the University of Edinburgh have collaborated and successfully developed a novel radiotracer, LW223. It selectively binds the TPSO with nanomolar affinity – a strong binding between the molecule and protein. It also has low toxicity to humans and can cross the blood-brain barrier. LW223 can therefore be used alongside PET imaging as a powerful diagnostic tool for a whole suite of diseases associated with TPSO, including stroke, brain cancer and myocardial infarction.

Two IAA projects supported the clinical development and commercialisation of LW223 for the imaging of inflammation-associated disease in humans:

In 2018, the first round of IAA funds was used to support the employment of an experienced organic chemist at the University of Glasgow for six months. To allow large-scale production of LW223, they improved the efficiency of its production by reducing the number of steps and improving the purity of the compound. The project also yielded analytical material, which enabled Advanced Biochemical Compounds (ABX) to prepare quantities of LW223 precursor for human trials. The Tavares group at the University of Edinburgh used these to begin human trials. This project was co-sponsored by Life Molecular Imaging (LMI), who, at this stage, signed a pre-licensing agreement to commercialise LW223.

A second IAA award in 2022 employed an organic chemist for four months, who used the previously optimised synthetic route to generate additional quantities of LW223’s precursor and standard. LMI used this material to start developing the commercial manufacture of LW223 and to further test preclinical models at their facilities. Additional quantities of LW223 precursor and standard were sent to McGill University in Canada, which had been subcontracted to conduct human trials with healthy patients.

Outcomes

  • Development of a PET imaging agent that will allow the early diagnosis of a range of inflammation-associated diseases, resulting in improved treatment.
  • Early commercialisation of a PET imaging agent that has the potential to generate substantial revenue.
  • Follow-on funding awarded to the Sunderland and Tavares groups in the form of a Developmental Pathway Funding Scheme (DPFS) grant from the Medical Research Council (MRC) for human trials with healthy volunteers and patients who have suffered myocardial infarction (£2.4M).
  • The LW223 project was used as an exemplar in a successful MRC facility grant application for a cutting-edge, total-body PET scanner for central Scotland, located at Edinburgh Royal Infirmary (£17M).
  • Pre-license agreement and initial financial support from our industrial partner, LMI, who will accelerate their commercial manufacture of LW223 after the successful completion of clinical trials.
  • Engagement with patients and the public through open days and science festivals.
  • Training and development of two postdoctoral researchers.

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