We are happy to announce that GLINT has successfully concluded its second reporting period. All workpackages have made considerable progress and are working towards the overall objective to develop a new, non-invasive MRI method using native D-glucose and 3-O-methyl-Dglucose (3OMG) as non-radioactive tracers to assess cancer glucose uptake and metabolism.
WP1: The WP1 partners ensured that an appropriate project management structure and governance, reflecting the project’s needs was set up in agreement with all partners. WP1 activities covered all aspects of project monitoring, reporting, financial and contractual administration in accordance with the Commission’s rules, ensuring proper communication within the consortium and implementing the project governance’s decisions.
WP2: For glucoCEST a robust dynamic imaging is needed, as well as a presaturation with minimal direct water saturation. To achieve this, we developed a snapshot CEST MRI method, consisting of a novel adiabatic spin-lock preparation phase and a fast 3D snapshot readout.
WP3: Using the modelling and analysis of compartmental models for different types of glucose uptake in the body, a CEST data processing software using Olea Sphere® Software Development Kit (SDK) was designed and implemented to process glucoCEST, APT and Iopamidol-CEST data. The software performance was tested on data provided by GLINT partners.
WP4: In order to separately assess glucose uptake and metabolism, both native and methylated glucose were measured together with a clear delineation of the in vivo characteristics of the metabolic pathway. The rate of mutarotation was found to be very long up to several days at low temperatures. The anomeric ratio at equilibrium was estimated to determine the pH in tumours, showing low to moderate/high correlation between the two image-based metrics in different regions of the tumours.
WP5: 3OMG was tested to detect tumours in several breast cancer models of murine and human origin, for different routes of administration of 3OMG and to compare the method with glucoCEST and with 18FDG‐PET on the same animals. In vitro D-Glucose provides higher CEST contrast at lower pH values, whereas 3OMG provides higher CEST contrast at pH 7.0-7.4 independent from B1 saturation power level. At 7T and 37°C, the detection threshold was found to be ca. 5 mM for 1 µT B1 and intravenous administration with 1.5 g/Kg produced enough detectable glucoCEST contrast in vivo.
WP6: A GMP-like batch was released to BCO in December 2017 and the first part of nonclinical safety studies reports has been concluded. Moreover, requests for ethical approval for GLP pharmacokinetics, biodistribution and excretion studies in rodents have been submitted to Italian Ministry of Health on 13 December, 2018.
WP7: Positive signal was observed only in brain of four patients, but not in three adult lymphoma patients and one prostate cancer patient. It was found that the signal-to-noise ratio is not high enough to obtain a signal outside the brain possibly due to lower glucose delivery and outside cancer types with large vascular components.
WP8: During the second period, WP8 carried out scientific and non-scientific dissemination activities at international meetings and events. The project’s knowledge management strategy was fully implemented and steps were taken for the protection of newly generated knowledge. Moreover, efforts to monitor the scientific findings to identify marketable results continued and preparations started for the development of a final exploitation strategy for GLINT (D8.4).
WP9: This Work package was automatically generated by the European Commission’s online system to track the completion of the Ethics Requirements. Eighteen deliverable reports were completed to ensure that all the activities carried out in the GLINT project comply with ethical principles and relevant national, EU and international legislation.