Non-invasive oximetric imaging of orthotopic glioblastoma tumors in mice

Glioblastoma multiforme is one of the most common intracranial tumors. It is distinguished by a high degree of malignancy and aggressiveness. It is difficult to diagnose and treat, which is why it is so important to introduce new therapeutic solutions that will enhance the effects of treatment and more accurately visualize neoplastic changes in the brain. Several treatments, including radiotherapy and PDT, strongly rely on the presence of oxygen before and during the therapy. Moreover, the changes in tumor oxygenation post-treatment have prognostic significance in the outcome of photodynamic therapy. The aim of the study was to measure non-invasively oxygen partial pressure (pO2) in an orthotopic model of glioma in mice. For this purpose, electron paramagnetic resonance (EPR) imaging with microspheres based on lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) was used. Mapping the oxygen concentration in tumor tissue is possible because tumor cells were mixed with LiNc-BuO crystal microspheres before implantation into the brain. The murine glioma cell line GL261 was used to inoculate a brain tumor in C57bl/6J mice orthotopically. The probe microcrystals containing unpaired electron spins allow for obtaining a repeated oxygen concentration from a small area around the site of tumor cell implantation. This can be corelated with anatomical magnetic resonance (MRI) images visualizing the size of the glioma tumor. In order to induce the photodynamic effect, it is planned to use nanoparticles that can cross the blood-brain barrier. This solution seems to be a great way of delivering drugs directly to brain tumors. AGuIX nanocarriers with a TPP photosensitizer are linked to a peptide that specifically binds to endothelial cells of blood vessels supplying blood to the tumor. After irradiation with 650 nm light, a photodynamic action of photosensitizer destroys the tumor's vascularization, thus depriving cancer cells of nutrients and changing the oxygenation level of the tumor. Oxygen partial pressure mapping of brain tumors brings an understanding of the degree of oxygenation of gliomas in the orthotopic model and in the future will provide valuable information that will allow tracking of the effectiveness of the therapy. Non-invasive methods of measuring pO2 in tumors may have immense potential in assessing the degree of effectiveness of anti-cancer therapies. ACKNOWLEDGEMENTS: NCBiR grant no DWM/ENM3-IV/425/2021