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Monitoring cancer heterogeneity based on the dynamic assessment of the Warburg effect under metabolic perturbation

Project description

Metabolic imaging in cancer diagnostics

Cancer diagnosis and treatment monitoring rely on molecular imaging methods which, however, cannot fully portray disease heterogeneity. To address this problem, the EU-funded CHyMERA project proposes to develop a novel technology that can image cancer phenotypes. The approach measures the kinetics of glucose flux through different metabolic pathways under different tumour microenvironment conditions and their association with cell proliferation. The CHyMERA methodology has a strong potential for clinical translation and is expected to improve specificity to cancer diagnosis and monitoring of treatment response.


Cancer heterogeneity is reflected in the multitude of phenotypes found in the clinic, with different proliferation statuses and metastatic potentials. These features cannot be assessed with the molecular imaging methods commonly available for diagnosis and monitoring. The main goal of this proposal is to develop a molecular imaging methodology based on endogenous contrast – CHyMERA – and demonstrate its feasibility to image hotspot areas of active proliferation and metastatic potential. The approach is based on the concept of cancer metabolic plasticity, does not require contrast agents or radioactive tracers, and should ultimately provide more specificity to cancer diagnosis and treatment planning than other imaging methods currently available. We propose to use animal models of human cancer, a glucose-enhanced imaging method, and an objective analysis of regional metabolic responses to controlled, reversible changes in the tumour microenvironment (perturbations), such as transient hypoxia. Specifically, we will (i) develop and validate CHyMERA at ultra-high magnetic fields, to monitor the metabolic kinetics of glucose and lactate in the tumour microenvironment. This methodology will be (ii) applied in vivo to two immunocompetent mouse model of GBM (allograft and genetically engineered models), to image vascular permeability/perfusion and hotspots of glioma proliferation. Finally, we will (iii) carry out a pilot study with two isogenic mouse models breast of cancer, metastatic and non-metastatic, to generate hotspots maps of proliferation and metastatic potential. All in vivo results will be validated post-mortem by immunohistochemistry. If successful, this methodology has a strong potential for clinical translational, which the host institution is ideally suited to test.


Net EU contribution
€ 159 815,04
Avenida brasilia, centro de investigacao da fundacao champalimaud
1400-038 Lisboa

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Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
Other funding
€ 0,00