Mapping Tumor Metabolic Aggressiveness with hybrid PET/MR Shift Reagents In Vivo

01.05.2023 bis 30.04.2026

The age-adjusted survival rate of cancer patients increased only 5%
since the 1950s, despite substantial advances in early detection
technologies. As such, there is an urgent need to develop reliable
biomarkers and personalized diagnostic tools that enable clinicians to
predict, non-invasively, the natural history and plasticity of tumor
masses. Using sensors capable of detecting specific extracellular
events in cancer, we can evaluate metabolic profiles detailed to each
tumor type—virtually in vivo non-invasive biopsies of the tumor
stroma. Exciting preliminary data from the team show that a novel
extracellular lactate sensor used together with advanced biomedical
imaging can detect extracellular lactate as a reliable biomarker for
cancer aggressiveness without significant interference from other
endogenous biomolecules. To our knowledge, this is the first-time
extracellular lactate produced by cancer cells could be detected in
vivo. Since overproduction of extracellular lactate is a hallmark of
cancer, via the Warburg effect—we propose a direct strategy to detect
the stages of tumor aggressiveness by utilizing novel hybrid metabolic
sensors (SRs*), state-of-art hybrid imaging, multiparametric data
analysis, and quantitative metabolic imaging. The success of the
proposed work plan will lay the foundation for further research in:
Design of probes detecting metabolic and functional events in the
microenvironment; accurate tumor phenotypic profiling with hybrid
probes; personalized and specialized diagnostic with multimodal
approaches; detection of disease progression (i.e. aggressiveness,
staging); quantitative metabolic imaging by the use of optimized
hybrid PET/MRI sensors aimed at translational studies; advanced
multiparametric analysis. This will ultimately lead to a holistic
understanding of cancer progression, metastasis, the associated
cancer aggressiveness, heterogeneity, and metabolic modulation in
solid tumors.