Metabolic Clustering and Modulation of the Tumour Microenvironememt
Understanding tumor microenvironment, heterogeneity, and metabolism will provide critical insights that will lead to symptomatic improvement of the diagnostic and to personalized cancer therapies. We aim to address the challenges associated with tumor heterogeneity and aggressiveness with novel hybrid positron emission tomography / magnetic resonance imaging (PET/MRI) sensors, state-of-the-art hybrid imaging, multiparametric data analysis & machine learning, and a quantitative functional imaging sensing approach. Our expertise will open venues to understand and modulate - with inhibitors currently undergoing clinical trials - tumor heterogeneity, aggressiveness, and malignancy. It will also create opportunities for the development of personalized treatments through specialized diagnostic methods capable of detecting relevant metabolic biomarkers (e.g., metabolites, pH, signaling metals, reactive oxygen species).
Quantitative Functional Imaging Metabolic Sensors
The development of “smart” and responsive multimodal sensors that detect events in the extracellular space offers the possibility of adding accurate molecular imaging information in addition to outstanding temporal and spatial resolution. Here, we combine expertise from several colleagues at the Radiochemistry group to design the next generation of functional quantitative imaging probes (e.g., hybrid PET/MRI sensors). We aim to develop sensors that detect changes in specific enzymatic activity, temperature, metal ion concentrations, oxygen pressure, and reactive species, pH, and metabolites. The Department of Preclinical Imaging and Radiopharmacy has state-of-the-art instrumentation ideal for this research (hybrid PET/MRI, PET/CT, and SPECT/CT scanners), modern small animal imaging facilities, GMP-capable radiochemistry with fully equipped laboratories which enable finally a clinical translation.
Metal Metabolism for Medical Imaging
Perturbed metal homeostasis is associated with pathological conditions such as dementia, cancer, and inherited metabolic abnormalities. Intracellular pathways involving essential metals have been extensively studied. However, whole-body fluxes and transport between different compartments remain poorly understood. Recently we have demonstrated in a collaborative effort with the Harvard Medical School and the UT Southwestern that zinc and copper play a critical role in identifying stages of malignancy in prostate cancer (PCa) by MRI and synchrotron radiation X-Ray fluorescence (SR-XRF) (Jordan et al., Inorg Chem. 2019 Oct 21;58(20)). Preliminary results from the WSIC also suggest that copper, zinc, and manganese play an essential role in triple-negative breast cancer, pancreatic cancers, and hepatocellular carcinomas (HCC). We aim here at the preclinical translation of metal metabolism using hybrid molecular imaging, personalized diagnostics, and specialized methods developed in-house: PET/MRI, HyperPET, functional quantitative imaging, PET/MRI sensors.