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

Published online by Cambridge University Press:  02 December 2014

David Mathieu ,
Roger Lecomte ,
Ana Maria Tsanaclis ,
Annie Larouche  and
David Fortin
David Mathieu
Affiliation:
The Department of Surgery, Division of Neurosurgery and Neuro-oncology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke University, Sherbrooke, Quebec, Canada
Roger Lecomte
Affiliation:
Department of Radiobiology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke University, Sherbrooke, Quebec, Canada
Ana Maria Tsanaclis
Affiliation:
Department of Pathology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke University, Sherbrooke, Quebec, Canada
Annie Larouche
Affiliation:
The Department of Surgery, Division of Neurosurgery and Neuro-oncology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke University, Sherbrooke, Quebec, Canada
David Fortin
Affiliation:
The Department of Surgery, Division of Neurosurgery and Neuro-oncology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke University, Sherbrooke, Quebec, Canada
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Abstract

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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.

Résumé:

RÉSUMÉ:

Standardisation et caractérisation détaillée du modèle de gliome syngénique Fischer/F98.

Contexte:

Nous avons besoin de modèles animaux adéquats pour la recherche préclinique sur le gliome en neuro-oncologie. Plusieurs modèles d'implantation ont été décrits, mais aucun ne correspond parfaitement aux gliomes malins chez l'humain. Nous rapportons notre expérience de standardisation, d'optimisation et de caractérisation du modèle de gliome Fisher/F98 du point de vue clinique, anatomopathologique, radiologique et métabolique.

Matériels et méthodes :

Des cellules F98 ont été implantées chez 70 rats Fisher, tout en variant la quantité de cellules et le volume de solution d'implantation au moyen d'une pompe à microinfusion afin de minimiser le traumatisme dû00E0; l'implantation, après avoir établi des paramètres adéquats. En anatomopathologie, nous avons utilisé la coloration H&E et l'immunohistochimie pour la GFAP, la vimentine, l'albumine, le TGF-b1, le TGF-b2, le CD3 et le CD45. Douze animaux ont subi une IRM aux jours 5, 10, 15 et 20. Les images ont été comparées aux lame histopathologiques correspondantes. On a procédé à des études au moyen du PET scan avec les traceurs 18F-FDG et 11C-acétate afin d'étudier le métabolisme des tumeurs chez deux animaux.

Résultats :

Les animaux chez qui on a implanté 1x104 cellules ont eu une survie médiane de 26 jours et une prise d'implant de 100%. Àla coloration H&E, on a observé de larges néoplasmes infiltrants avec un centre nécrotique, ainsi que de nombreuses mitoses, un comportement infiltrant péritumoral et une prolifération néovasculaire. La coloration pour la GFAP et la vimentine étaient positives dans les cellules tumorales. La coloration pour l'albumine était positive dans les espaces extracellulaires autour des tumeurs. La coloration CD3 était négligeable. L'IRM était corrélée aux observations anatomopathologiques. La captation du 18F-FDG dans les tumeurs était importante.

Conclusion :

Le modèle standardisé décrit dans cette étude se comporte de façon prévisible et reproductible et pourrait être utilisé à l'avenir dans les études précliniques. Il simule adéquatement le comportement des astrocytomes malins de l'humain.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 3 , August 2007 , pp. 296 - 306
Copyright
Copyright © The Canadian Journal of Neurological 2007

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