Descrizione del progetto
Imaging metabolico nella diagnostica oncologica
La diagnosi del cancro e il monitoraggio del trattamento si basano su metodi di imaging molecolare che, tuttavia, non sono in grado di rappresentare l’eterogeneità della malattia. Per affrontare questo problema, il progetto CHyMERA, finanziato dall’UE, introduce lo sviluppo di una nuova tecnologia capace di rilevare i fenotipi tumorali. Tale approccio misura la cinetica del flusso di glucosio attraverso diversi percorsi metabolici in differenti condizioni del microambiente tumorale e la loro associazione con la proliferazione cellulare. La metodologia di CHyMERA dispone di un notevole potenziale per l’utilizzo in ambito clinico e si prevede che migliori la specificità della diagnosi del cancro e il monitoraggio della risposta al trattamento.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
1400-038 Lisboa
Portogallo