An improved F98 glioblastoma rat model to evaluate novel treatment strategies incorporating the standard of care

Glioblastoma (GB) is the most common and malignant primary brain tumor in adults with a median survival of 12-15 months. The F98 Fischer rat model is one of the most frequently used animal models for GB studies. However, suboptimal inoculation leads to extra-axial and extracranial tumor formations,...

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Bibliographic Details
Published in:PloS one 2024-01, Vol.19 (1), p.e0296360-e0296360
Main Authors: Zoteva, Velislava, De Meulenaere, Valerie, De Boeck, Marthe, Vanhove, Christian, Leybaert, Luc, Raedt, Robrecht, Pieters, Leen, Vral, Anne, Boterberg, Tom, Deblaere, Karel
Format: Article
Language:English
Subjects:
Animal models
Animals
Biology and Life Sciences
Brain cancer
Brain Neoplasms - pathology
Brain tumors
Cancer
Care and treatment
Chemotherapy
Diagnosis
Engineering and Technology
Glioblastoma
Glioblastoma - pathology
Glioblastoma multiforme
Glioma
Health aspects
Inoculation
Magnetic resonance imaging
Medical prognosis
Medicine and Health Sciences
Patient outcomes
Performance evaluation
Prognosis
Radiation therapy
Radiotherapy
Radiotherapy Dosage
Rats
Rats, Inbred F344
Research and Analysis Methods
Standard of Care
Temozolomide
Translation
Tumors
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Summary:Glioblastoma (GB) is the most common and malignant primary brain tumor in adults with a median survival of 12-15 months. The F98 Fischer rat model is one of the most frequently used animal models for GB studies. However, suboptimal inoculation leads to extra-axial and extracranial tumor formations, affecting its translational value. We aim to improve the F98 rat model by incorporating MRI-guided (hypo)fractionated radiotherapy (3 x 9 Gy) and concomitant temozolomide chemotherapy, mimicking the current standard of care. To minimize undesired tumor growth, we reduced the number of inoculated cells (starting from 20 000 to 500 F98 cells), slowed the withdrawal of the syringe post-inoculation, and irradiated the inoculation track separately. Our results reveal that reducing the number of F98 GB cells correlates with a diminished risk of extra-axial and extracranial tumor growth. However, this introduces higher variability in days until GB confirmation and uniformity in GB growth. To strike a balance, the model inoculated with 5000 F98 cells displayed the best results and was chosen as the most favorable. In conclusion, our improved model offers enhanced translational potential, paving the way for more accurate and reliable assessments of novel adjuvant therapeutic approaches for GB.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0296360