MITIGATE End-User Survey
Participate in our End-User Survey and help us to bring MITIGATE`s innovative results to the European patient!
The FP7 project MITIGATE will develop a closed-loop molecular environment for minimally invasive treatment of patients with metastatic Gastrointestinal Stromal Tumours (GIST). The MITIGATE consortium representing three European universities, three research organisations and four SMEs will pursue the ultimate goal to develop new protocols and guidelines to effectively diagnose and treat patients with metastatic GIST resistant to current treatment.
In order to gain a better understanding of how the community might want to exploit our innovative results we have set up a set of short and user friendly surveys tailored to end user interests and fields of research.
Below you will find a short description about the either already obtained or envisaged results and the link to the respective survey. If more fields of expertise match your profile, please also fill in the second and third survey and support us in bringing the MITIGATE products to the European patient.
SURVEY 1: Nuclear medicine: biodistribution for tracer/probe development
The MITIGATE project will develop and implement a physiologically based pharmacokinetic (PBPK) model for the simulation and prediction of human biodistribution and absorbed doses using mice biodistribution data. As a first step, the model will use murine biokinetic data of tumour, kidney, liver and spleen, together with the amount of injected substance and activity, as input. After determining the adjustable fitting parameters for the corresponding xenograft in a second step, the model parameters, e.g. blood flows and organ masses, are changed from mouse to human. For this human model, the user can add the receptor density and volume of the human tumour as additional parameter, and simulate the human biodistribution. The output, the time-integrated activity coefficients, can then be used to calculate the expected absorbed doses. Different amounts of injected amounts and activities can be simulated to determine a suitable first-in-man-dosage.
SURVEY 2: GIST and tumour endoscopy and tissue isolation/dissociation
Standard endoscopic biopsy procedures require high human effort and skill. Furthermore, a consistent quality of biopsies is often not achieved due to different methods between surgeons. To ensure a more standardised procedure, the MITIGATE project developed a novel endoscopic biopsy system. It enables physicians to sample tissue from submucosal tumours using a flexible endoscope. The biopsy device can be directly combined with a tissue dissociation module to allow specific cell isolation and subsequent analysis of the biopsy.
SURVEY 3: Tissue and biofluid analysis
MITIGATE developed novel procedures for the analysis of tissues and biofluids based on mass spectrometry. For diagnostic purposes, analysis services for processing biofluid samples (like blood or urine) and tissue samples from biopsies or resections can be offered. Based on mass spectrometry measurements, molecular information of the sample is acquired which can be used for a detailed characterisation of the tissue or biofluid. For example, information about metastasis mutation and even prediction of response to medication. In contrast to existing technologies, mass spectrometry measurements are not specific to a single target. This technique can be used to support the diagnosis and therapy of a broad range of diseases.
SURVEY 4: GIST and cancer imaging
Currently, there are no dedicated and specific procedures available for GIST imaging. The MITIGATE project has developed a novel approach for the radiopharmaceutical preparation of 68Ga-labelled peptides. This approach is used to produce a PET diagnostic agent for GIST imaging under the name NeoBOMB1. The NeoBOMB1 peptide binds with high affinity to the Gastrin Releasing Peptide Receptors (GRPR) overexpressed in GIST tumours and can be efficiently labelled with the metallic positron emitter Gallium 68 (68Ga). This radionuclide has attracted interest and it is being increasingly employed as a radionuclide for PET imaging, thanks to its radiochemical characteristics (68 min half-life, high positron emission yield) and the large availability of 68Ge/68Ga generators, which makes its production independent from cyclotrons. The advantages of such a tracer and its innovative aspects are the following:
- The 68Ga-labelled NeoBOMB1 is a molecular PET imaging probe that targets a specific class of receptors (GRPR), overexpressed on GIST cancer cells (as compared to 18F-FDG, for example, whose uptake is based on a metabolic process)
- The novel approach guarantees a straightforward, reproducible and accessible radiolabelling procedure, allowing for direct reconstitution of the NeoBOMB1 peptide with the Gallium-68 solution obtained from commercially available generators, without the need of additional steps for product purification.
In addition to the PET-based approach, MITIGATE is also developing quantitative imaging with novel functional magnetic resonance imaging (fMRI) protocols for the assessment of drug resistance. Using these fMRI protocols it is possible to characterise TKI-sensitive and TKI-resistance GIST tumours. The developed protocols are based on T2w, DCE, CEST, DWI and 23Na X-MRI imaging.