Project description

Facts and figures

Acronym:	GLINT
Start date:	January 1st, 2016
Duration:	48 months
End date:	December 31st, 2019
Project coordinator:	Prof. Xavier Golay, UCL
Consortium:	8 partners - major universities, research institutes and industry - from 7 countries
Total funding:	€6,454,612

Context

Cancer accounts for 13% of all deaths worldwide and despite recent medical improvements remains one of the most deleterious diseases in the world. Early detection is very important as it increases the chances of survival. Presently, cancer is detected, staged and followed-up through advanced medical imaging, e.g. computer tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). This high level of sophistication towards treating cancer has generated a new problem: the differentiation between treatment effect, regrowth or pseudo-progression of the tumour, which are all poorly differentiated on most imaging methods.

The GLINT project addresses the current global lack of safe, cheap, easily accessible and accurate image-based metabolic evaluation techniques to detect cancer and will develop an innovative method which will allow for more accurate, less invasive, more reliable and earlier cancer diagnosis.

Objectives

GLINT aims to establish the GlucoCEST imaging of neoplastic tumours and bring the combination of native D-glucose and 3-O-methyl-D-glucose as a combined exam to European clinical oncology practice to assess cancer glucose uptake and metabolism in almost all cancer types, thereby providing a wide-ranging new diagnostic tool for one of the most devastating diseases in the world. A major deliverable of the project is to provide a cheap, widely available, more comprehensive, non-invasive, radiation-free complementary method to nuclear medicine techniques currently used for cancer assessment within Europe.

More specifically, the project aims to:

Improve the detection of non-radioactive tracers (glucose and analogues) using MRI techniques and increase availability and ease-of-use of these methods in oncology clinics across Europe.
establish the safety profile of GMP-grade 3-O-methyl-D-glucose as a non-invasive, cheaper and more readily available reporter of glucose uptake in cancer
establish native D-glucose in GlucoCEST MRI as a means to define diagnostic properties for assessing cancer progression in several cancer models
establish detection thresholds and response to therapy in animal models of solid cancers
demonstrate efficacy and safety of the GlucoCEST method using native glucose through extensive testing in human neoplasms
exploit GLINT's results to commercialize combined examinations of D-glucose and 3-O-methyl-D-glucose in the clinics
develop and commercialize integrated software for the detection and analysis of glucose MRI in the clinic
Collaborate with European regulatory bodies through the European Society of Radiology's European Imaging Biomarkers Alliance (EIBALL), to aid in European integration of the technique as part of the future pan-European clinical guidelines for cancer diagnosis.

Project output and deliverables

GLINT will develop the following output and exploitable deliverables, representing significant innovation potential:

An advanced MR imaging technique, allowing robust detection of the small exchange-related signal on clinical scanners. In particular, we will explore the possibility to combine CEST with other MRI methods to improve detection of glucose and glucose analogues and reduce acquisition times.
Pharmacokinetic analysis for quantification of GlucoCEST effect in vivo. While the original GlucoCEST experiments performed at UCL were quasi-static, here we propose to sample the data at a high temporal rate and allow for full pharmacokinetic modelling of the data upon infusion of glucose or glucose analogues at different concentrations
Assessment of potential biochemical pathways and the sources of the GlucoCEST signal for native and methylated glucose analogues
Validated detection thresholds and therapy response of the glucose analogues (in animal models)
Regulatory approvals packages for all used tracers, including toxicology, biodistribution, pharmacokinetics of 3OMG.
Assessment of the sensitivity, specificity staging, early prediction to therapy and evidence of treatment effects in glioma, head and neck squamous cell carcinoma, or lymphoma as cancer models in patient studies

Impact

GLINT will develop a completely new technique, based on the non-invasive detection of native glucose first by glucoCEST in patients suffering from three different types of cancer: squamous cell carcinoma, paediatric lymphomas and primary gliomas.

Overall, the GLINT project will contribute significantly to the sustainability of healthcare systems throughout Europe. The development and commercialisation of glucoCEST MRI as an innovative in vivo new metabolic imaging technique will enable personalised healthcare for cancer treatment by providing a cheap metabolic imaging alternative and benefit the global cancer population by improving the diagnostic accuracy of MRI and providing early readouts of treatment efficacy, leading to improved clinical decisions and outcomes while expected costs per patient are expected to be 6-10 times cheaper than of current techniques.

This game-changing technology, based on MRI, will be able to image glucose delivery, uptake and metabolism in cancer, using a combination of native non-labelled glucose with methylated glucose (3-O-Methyl-D-Glucose). Patients will benefit from improved treatment outcomes and earlier access to novel therapies. Pharmaceutical industries will benefit from a reduced time-to-market of new drugs through improved success rate of clinical trials by enrichment of particular cancer subtypes; reduced number of patients per trial; reduced treatment time by cutting of the trial-and-error phase of treatments for patients; and provision of a safer, cheaper and more widely available imaging method for use in clinical trials. In addition, the use of the same high-resolution glucoCEST imaging technique as biomarker can be applied in both animal models and cancer patients allowing refinement of therapies by back translation from patient tissue characterisation to mice models.

This newly developed technology will be more accurate than the current standard, ¹⁸F-FDG-PET, as it allows the separation between glucose uptake and metabolism. It will also clearly be less invasive, as radiolabelled compounds are not required. Additionally, current technology used in daily clinical practice is only semi-quantitative, while our technology will be based on a quantitative pK-analysis of the glycolytic pathway, and will therefore be more reliable. These advantages are going to lead our technology to be more predictive of disease outcome. In addition, it will be easier to use to follow early response to therapy, as it will not be limited by a total radiation dose, which limits the current PET-based techniques.

Finally, the non-radioactive imaging of glucose metabolism through glucoCEST MRI will also open the field of metabolic imaging for a multitude of non-cancer diseases. The GLINT project will help develop other MRI techniques, thereby increasing the potential applications of this important diagnostic tool.