The combined Cubresa PET/MRI system has been a crucial tool in advancing our understanding of adoptive cell therapy of brain tumors. These studies exploit the sensitivity of PET to define the spatial distribution of adoptively transferred immune cells and the specificity of MRI to delineate brain tumors and their responses to therapy. Over the last few months, we have utilized the Cubresa PET/MRI system to study the trafficking of adoptively transferred T cells expressing chimeric antigen receptors (CAR T cells) in a mouse glioma model. One of most important and clinically relevant parameters in this disease model is determination of the optimal route of CAR T cell infusion and understanding their trafficking and persistence post-infusion. To this end, combined PET/MRI has provided critical spatio-temporal information revealing the position of Zr-89 labeled CAR T cells within the brain following intratumoral and intraventricular delivery. MRI also delineates brain tumors and provides an assessment of response to therapy, as inferred by anatomical changes within the malignancy and co-localization of adoptively CAR T cells.
We have also utilized the PET/MRI system to evaluate PET tracers for leptomeningeal disease. Specific accumulation of metabolic PET radiotracers within the meninges of the brain is confirmed by co-registration with anatomical MRI of the brain. Future studies will expand the use of PET/MRI to NK and CAR T cell therapy models of other solid tumors such as osteosarcoma. These studies will similarly utilize PET to image adoptively transferred Zr89-labeled immune cells and MRI to delineate tumor tissue and assess responses to cell therapy. Other studies will utilize this tool in mouse models of brain metastases to assess the capacity of PET radiotracers in diagnosing and monitoring responses to therapy.