Abstract
Abstract BACKGROUND Glioblastoma are aggressive and incurable primary tumors of the central nervous system. As patients present with already established tumors, longitudinal imaging by MRI and [18F]FET-PET in human glioblastoma for characterizing temporal and spatial metabolic alterations is only possible to characterize alterations during therapy, but not during tumor evolution. In this regard, genetically engineered preclinical models are very relevant. The replication-competent avian sarcoma-leukosis virus (RCAS)/tumor virus receptor-A (tva) system provides a high grade of spatial and temporal control of somatic gene delivery in vivo. In this study, we used longitudinal MRI and [18F]FET-PET to characterize the evolution and growth of platelet-derived growth factor B (PDGFB)-driven glioma model using the RCAS-tva system. MATERIAL AND METHODS DF-1 cells transfected with PDGFB were implanted into adult 129S.Tg(NES-TVA)-Cdkn2a−/− mice intracranially. Mice received MRI twice and [18F]FET-PET measurements once per week. Longitudinal growth pattern and [18F]FET-PET uptake were assessed and analyzed. We measured symptom-free survival and performed immunohistochemistry on collected tumor tissue samples. RESULTS We observed robust tumor formation with highly reproducible symptom-free survival times of treatment-naïve experimental animals. Contrast-enhanced MRI volumetry revealed exponential growth dynamics starting around day 25 after DF-1 inoculation. Here, the PDGFB-driven gliomas present an escalating [18F]FET-PET uptake as well as increasing BBB permeability over time. These imaging features match the clinical scenario, which underlines the translational relevance of this model. Histology corroborated the imaging findings and an immunogenic glioma-associated microenvironment. CONCLUSION These data provide further valuable insights into this RCAS/tva-based PDGFB-driven murine glioma model and advocates for an imaging-stratified design of preclinical therapeutic interventions.
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