This Work Package is tasked with the effective administration, management and governance of the GLINT Project across all GLINT project partners. This incorporates duties covering all aspects of project monitoring, reporting, financial and contractual administration according to the Commission’s rules, ensuring proper communication within the consortium and implementing the project’s governance and decision-making structures as laid out in Description of Action. The specific objectives of this Work Package are:
This work package is dedicated to the development of advanced MR imaging techniques across the European centres involved in the project, allowing robust detection of the small exchange-related signal on clinical scanners (3T Siemens PRISMA and MMR scanners and experimental 9.4T human scanner) and for animal scanners in WP4. The methods developed within the WP will take advantage of the rapid exchange protons of the hydroxyl groups of glucose molecules with the water and its effects on all physical relaxation rates present in an MRI experiment, including T1, T2, and T1ρ.
Objectives of the work package will thus include:
The main objectives of this Work Package are to establish the entire post-processing pipeline for all MRI experiments undertaken within the GLINT consortium. This will be lead by OM in collaboration with 5 other partners of the GLINT consortium, to ensure that all algorithms will be tested on real data prior to the distribution of the Software through the Olea-SphereTM package to every group in Europe and the world who wants to use it. The development of new applications for the post-processing of emerging MR sequences is a strategic issue for OM, since the company intends to keep up competitively with the development of MR physics. Therefore the primary outcome of this work package will help one of the most successful SME within Europe, OM, to increase its offer and therefore bring them some definitive advantage over the competition. For this to happen, the following three objectives are set:
The main objective of WP 4 will be to assess the potential biochemical pathways and the sources of the GlucoCEST signal for native and methylated glucose analogues. The results from this WP will allow to us to properly define the pK used in WP 3. The following sub-aims are also defined:
The main objective of WP5 is to establish the detection limits of the candidate molecules selected in WP3 for both in vitro and in vivo conditions. In in vitro conditions, the following effects will be evaluated for discerning and optimizing the achievable CEST contrast: probe concentration; pH; temperature; magnetic field strength. For in vivo evaluation, representative tumour models will be selected and the influence of the following parameters will be evaluated: injected dose; administration route; magnetic field strength.
A second objective is devoted to exploit these molecules as early reporter of a therapeutic effect. This includes the administration of conventional therapies and new anticancer therapies (inhibitors of tumour metabolism) on selected murine tumour models for assessing the capability of the GlucoCEST contrast to report on treatment response. The GlucoCEST derived response will be compared with the gold-standard [18F]FDG-PET imaging assessment to understand the role that this new proposed approach may have as an alternative imaging method. Moreover, other MRIbased modalities, such as changes in tissue cellularity, vascularisation and acidosis will be evaluated and compared to the GlucoCEST readout for its ability to assess the therapeutic response.
In Work Package 6 the following objectives are addressed:
Data from first-in-man studies in cancer patients will be acquired, based on the optimised imaging techniques developed jointly with MPG in WP 2 and the data analysed quantitatively using the models developed in collaboration with OM within WP 3. Main objective: for GlucoCEST to bridge the 1st translational gap as outlined in the world's largest independent cancer research charity (Cancer Research UK - CRUK) imaging biomarker roadmap by providing a detailed validation of GlucoCEST in patients in the EU, and quantify its utility in detecting and staging cancer, as well as predicting response to therapy. This will be done through:
To address the above, three different cohorts of cancer patients will be recruited from established referral pathways at the UCLH MacMillan Cancer Centre (£110m purpose built centre integrating care of cancer patients with cutting-edge clinical and radiological research) and the National Hospital of Neurology and Neurosurgery (NHNN) within UCL. In addition, patients suffering from primary brain tumour (glioma) will also be recruited from the Tübingen University Hospital through MPG. Each cohort will provide the substrate for validation; biomarker qualification will be targeted to address unmet clinical need to provide maximum clinical impact:
WP8 will develop and pursue the overall external project communication, dissemination and exploitation activities as well as knowledge management to raise scientific and public awareness and ensure uptake of the project work and outcomes across Europe. WP8 will demonstrate the benefits for all end-users. Input to this horizontal task will be required from all project partners.
In detail the objectives of this work package are to