Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

Abstract

Introduction:Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects.Materials and methods:F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGF-b2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18F-FDG and 11C-acetate PET studies for metabolic characterization of the tumors.Results:Implantation with 1x104 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings. 18F-FDG uptake was strong in the tumors.Conclusion:The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas.