Tumor Angiogenesis

Angiogenesis is commonly indicated as a hallmark of cancer. It involves the formation of new capillaries from pre-existing vessels for ensuring the blood support necessary to tumor expansion and metastasis to distant organs. In cancer biology, this process is highly deregulated. As a consequence, tumor vasculature displays a highly destructured and dysfunctional network, mainly characterized by hyperpermeability and reduced tumor perfusion. These structural features contribute to vascular heterogeneity and impair tumor blood flow responsible of hypoxia, interstitial pressure and acidosis. Therefore, several therapeutic strategies are under investigation tonormalize the tumor vasculature throughout antiangiogenic therapies for improving blood perfusion and for decreasing level of hypoxia that makes the cells resistant to radiotherapy and cytotoxic agents.
Several imaging techniques have been developed to visualize these structural abnormalities.

  • Dynamic Contrast Enhanced (DCE) MRI

    In our lab we develop MRI-based functional approaches in order to characterize tumor angiogenesis in several murine models and evaluate the response to pharmacological treatments. We mainly focus on DCE−MRI technique, that allows the visualization of tumor vasculature by exploiting the injection of pre clinical/clinical Gd3+−based contrast agents informative of tumor perfusion and permeability. In particular, we recently developed a novel blood pool agent (Gd-AAZTA Madec) able to provide an accurate quantification of intratumoral vessels at low magnetic field, therefore facilitating the translation of our approach. In combination with the superb anatomical resolution of MRI, this technique allows the implementation of dedicated tools able to analyse tumor heterogeneity and visualize its role in modulating the response to therapy.

  • DCE-CEST (Chemical Exchange Saturation Transfer) MRI

    In addition, our research recently focused on the development of MRI perfusion agents able to be detected by the chemical exchange saturation transfer approach (CEST) , in order to provide alternatives to Gd3+−based contrast agents.

  • Dynamic Contrast Enhanced Optoacoustic Imaging

    We are exploring also macromolecular biodegradable photoacoustic probes based on the natural plaftorm of melanin, to provide tumor vasculature information by means of photoacoustic imaging.

Group Leaders:

Dario Longo