THERAGLIO · Microbubble driven multimodal imaging and theranostics for gliomas

Microbubbles (MBs) are used as contrast agent in ultrasound (US) imaging for a variety of tumours while little has been done for glioblastomas, a rare cancer. Intraoperative Contrast-Enhanced US-imaging (CEUS) using lipidic MBs hold promises in increasing extent of resection of such tumors. Furthermore, MBs gained recently interest as a delivery system for drugs. We will develop a new generation of multimodal MBs, acting simultaneously as contrast agent for Magnetic Resonance Imaging (MRI), CEUS and intra-operative fluorescence for multimodal real-time image-guided resection of glioblastomas. We plan to transform MBs by replacing air with perfluorcarbon gas and/or attaching super-paramagnetic-iron-oxide nanoparticles for MRI visualization. We will also engineer MBs with RGD-motif to adhere selectively to pathological endothelial integrins and with near-infrared fluorophores for simultaneous US deep tissue imaging and direct microscopic tumour visualization to maximize resection. A software will be developed for integration of preoperative MRI, intraoperative US and microscopic imaging. We will focus on lipidic and polymeric MBs. Lipidic MBs are approved for clinical use; therefore, once modified, more easily translatable into clinical applications to reach a feasibility study on patients. In addition, we will improve multifunctional, polymer-based MBs. Multifunctional-stabilized-polymer-MBs are more stable and more versatile to be complexed with different molecules or nanoparticles as compared to lipidic Mbs and will be designed as a platform for delivering standard and/or experimental chemotherapeutic drugs to the tumour, acting as an innovative way for local targeting and delivering any kind of agent to a specific target, in a safe and controlled fashion. This would be a big step forward in the field of personalized medicine, moving standard MG image-guided treatment towards more effective, safer, molecular-based tailored interventions to specific patients.