This project addresses the challenge of diagnosing glioblastoma (GBM), a highly aggressive and lethal brain tumor. GBM treatment is complicated by the blood-brain barrier (BBB), a natural defense system that prevents over 98% of drugs from entering the brain, thus limiting the effectiveness of chemotherapy. Early diagnosis is also hindered by the BBB, as current imaging methods struggle to detect GBM at early stages. Positron Emission Tomography (PET) imaging, widely used for various cancers, has the potential to improve brain tumor diagnosis when combined with monoclonal antibodies (mAbs) targeting specific proteins in the tumor. However, delivering these antibodies across the BBB remains a major obstacle. This project focuses on developing nanocarriers capable of crossing the BBB to deliver radiolabeled mAbs, facilitating early detection through PET imaging.

The main objectives are to develop and optimize nanocarriers that are stable in the bloodstream, avoiding opsonization by minimizing the formation of a protein corona, and can efficiently cross the BBB to target GBM cells. Another objective is to radiolabel the mAbs with Zr-89 and evaluate their effectiveness in PET imaging. The project also aims to conduct thorough in vitro and in vivo studies to assess the ability of these nanocarriers to reach the brain, accumulate in GBM cells, and provide reliable imaging data.

The methodology is divided into four key work packages. The first one focuses on the design and optimization of synthetic nanocarriers composed of lipids, biopolymers, and penetration enhancers, along with a protective polymeric shell to prolong circulation in the bloodstream. These nanocarriers will be functionalized to bind receptors on the BBB, facilitating their transport into the brain. The second work package involves radiolabeling the mAbs with Zr89. The radiolabeling process will be carefully monitored to ensure the retention of the antibodies' targeting capability. The third one consists of in vitro studies to evaluate the toxicity, stability, and BBB-crossing efficacy of the nanocarriers using cell models that mimic the BBB. Finally, the fourth one focuses on in vivo biodistribution studies, using PET imaging to track the localization of nanocarriers and radiolabeled mAbs in animal models. These studies will help refine the design of the nanocarriers and ensure their efficiency in crossing the BBB and targeting GBM cells.

In summary, this project integrates advanced nanotechnology and molecular imaging techniques to develop a promising tool for the early diagnosis of GBM, potentially leading to more effective and personalized treatments for brain tumor patients