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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PET3D (PET Imaging in Drug Design and Development)

Teaser

Summary

There is a current shortage in Europe of scientists who can use special imaging tools such as Positron Emission Tomography (PET) that could speed up and reduce the cost of development of life-saving drugs. This represents a significant problem as PET imaging plays a key role in cancer, heart conditions and neurological diseases and is used by all the major pharmaceutical companies to identify effective drugs at a much earlier stage of drug development. Currently, only 10 in 10,000 drug candidates that enter pre-clinical testing progress to human testing, and only 1 out of those 10 molecules actually make it to the market. The failure of many of these molecules in Phase III, as opposed to Phase I and II trials, means that a lot of resources has been wasted getting to Phase III, only then to fail.

PET is a non-invasive and highly sensitive imaging technology developed to visualise and quantify biochemical and physiological processes in vivo. PET imaging can be used to address key questions such as what and where is the disease? Is the disease accurately targeted by the therapy? Is the treatment effective? The ability to answer these questions using PET imaging places scientists in a much more informed position to progress from pre-clinical testing to human testing, i.e. Phase III in drug development.

The PET3D (PET imaging in Drug Design and Development) project is a four-year innovative programme that focuses on training 15 Early Stage Researchers (ESRs) to become experts in PET and to equip them with the skills necessary to be able to apply PET imaging in an innovative way as a key technology for boosting cost effective drug design and development. We have brought together leading expertise from 6 European academic PET centres and 2 industrial organisations. Through regular network meetings and training schools each ESR is provided with a holistic and exceptionally fertile research and training environment. The entrepreneurial experience of the ESRs is also developed through secondments with our industrial beneficiaries. The PET3D consortium stimulates cross-fertilisation between the 15 different research projects, which share the same overall challenges in PET imaging technology. Thus, while the research work in PET3D is following 15 different research streams, together they form a single body of research heading towards the successful completion of the project that validates PET imaging as a paradigm-changing tool in drug design and development.

Work performed

The PET3D consortium addresses two main objectives: (i) the scientific programme and (ii) the training programme.

The activity of the consortium is structured around five work scientific workpackages (WP 1-5) and one network-wide training and dissemination WP (WP 6).
Each Scientific WP reflects a research theme and each WP contains 3 PhD interrelated PhD projects. To use PET to visualise biological processes in the body, various novel â€˜tracerâ€™ molecules need to be developed. These â€˜tracerâ€™ molecules should fully retain all the biological functions and characteristics.
The focus of WPs 1-3 is tracers in oncology, WP 4 is cardiovascular and WP 5 is the central nervous system (CNS).
The oncology WPs are exploiting three different strategies: WP1 is radiolabelling nanoparticles and small molecules or peptides, WP2 is focussing on radiolabelling different biologicals such as full antibodies and nanobodies and the focus of WP3 is an emerging state-of-the-art technology looking at pre-targeted labelling of protein-type targeting vectors.
WP4 involves the development of novel PET candidates that will be instrumental in detecting early heart failure and WP5 is centred on CNS pathologies such as ischemia and brain tumours (i.e. gliomas) in which PET tracers are required to cross the blood-brain-barrier.

So far, the PET3D consortium has been investigating and developing a number of novel PET tracers â€“ in different formats, such as small molecules, peptides, nano- and anti-bodies, nanoparticles â€“ and novel technology for introducing PET emitting nuclides (pre-targeting, in vivo chemistry). Currently these tracers are being studied for the potential to be used in drug development in a number of therapeutic areas, such as cancer, neurodegeneration, stroke, cardiovascular disorders.

WP6 involves network-wide training and dissemination, 3 network training events have been held to date. A 5 day school was held on Radiopharmaceutical development at VUMC, Amsterdam, The Netherlands; this involved lectures and 3 days of hands on experiments. A 2 day school on Radiopharmaceuticals in drug discovery was held at the AstraZeneca site in Molndal, Sweden which also provided an overview of the drug discovery and development process and a site tour. A 1 day training workshop was held at CIC-bioMAGUNE, San Sebastian, Spain. This event covered complementary and transferrable skills and addressed â€˜life after PET3Dâ€™ providing talks on writing grant applications and creating a biotech company. All ESRs have presented their scientific results at external conferences and workshops in the form or posters or oral communications. We also have 4 different articles published as listed on the PET3D website, two research articles, one scientific review and one Impact article in non-specialised press.

Final results

The primary aim of the PET3D project is to promote PET in Europe by training a new generation of PET imaging scientists. In particular, the PET3D programme exposes recruited researchers to a multidisciplinary and inter-sectorial environment, making the researchersâ€™ future careers more attractive due to the interaction between academia and industry.