Early detection of breast cancer lung metastasis with high precision using new nanoparticle-based PET imaging agents

Breast cancer is the second-leading cause of death in women worldwide, and >90% of deaths among cancer patients are due to metastasis where the lung is one of the organs into which most cancers metastasize. Therefore, it is of paramount importance to detect metastasis early enough with high precision. Positron emission tomography (PET) is a non-invasive and quantitative medical imaging technology with high sensitivity, but an unmet clinical need remains for novel radioactive drugs or imaging agents that can detect metastasis in a timely manner. In this project, we will develop novel agents targeting both stroma activation and tumour cells to achieve early PET detection of pre-metastatic niches and micrometastasis. Our strategy is to target folate receptors and fibroblast activation protein which are highly expressed in activated stroma and/or tumour cells, and use nanotechnology to intensify radioactivity signals in tumour lesions for detection. The mesoporous silica nanoparticle (MSN) platform we will use has been under development within the concerned group for two decades, and successful folate targeting of these has been demonstrated in multiple studies in vitro and in vivo. Here, we aim to establish a new NP radiolabeling strategy based on silicon-fluorine (Si-18F) radiochemistry without using conventional chelates. This will enable a more straightforward incorporation of radionuclides with higher efficiency, thus leading to increased signal intensity in PET imaging. This will ultimately yield radiolabelled MSNs as novel agents for clinical PET imaging and early detection and consequently, diagnosis of breast cancer metastasis. Overall, we hypothesize that it is possible to achieve early metastasis detection by the synergistic combination of targeting stroma activation and MSN-based signal enrichment, given that stroma has already become activated before tumour cell arrival. We will exemplify our strategies by using breast cancer lung metastasis model in mice.