NDLI: Contrast-enhanced, conebeam CT-based, fractionated radiotherapy and follow-up monitoring of orthotopic mouse glioblastoma: a proof-of-concept study

Content Provider	Springer Nature : BioMed Central
Author	Stegen, Benjamin Nieto, Alexander Albrecht, Valerie Maas, Jessica Orth, Michael Neumaier, Klement Reinhardt, Sabine Weick-Kleemann, Moritz Goetz, Wilfried Reinhart, Merle Parodi, Katia Belka, Claus Niyazi, Maximilian Lauber, Kirsten
Abstract	Background Despite aggressive treatment regimens comprising surgery and radiochemotherapy, glioblastoma (GBM) remains a cancer entity with very poor prognosis. The development of novel, combined modality approaches necessitates adequate preclinical model systems and therapy regimens that closely reflect the clinical situation. So far, image-guided, fractionated radiotherapy of orthotopic GBM models represents a major limitation in this regard. Methods GL261 mouse GBM cells were inoculated into the right hemispheres of C57BL/6 mice. Tumor growth was monitored by contrast-enhanced conebeam CT (CBCT) scans. When reaching an average volume of approximately 7 mm3, GBM tumors were irradiated with daily fractions of 2 Gy up to a cumulative dose of 20 Gy in different beam collimation settings. For treatment planning and tumor volume follow-up, contrast-enhanced CBCT scans were performed twice per week. Daily repositioning of animals was achieved by alignment of bony structures in native CBCT scans. When showing neurological symptoms, mice were sacrificed by cardiac perfusion. Brains, livers, and kidneys were processed into histologic sections. Potential toxic effects of contrast agent administration were assessed by measurement of liver enzyme and creatinine serum levels and by histologic examination. Results Tumors were successfully visualized by contrast-enhanced CBCT scans with a detection limit of approximately 2 mm3, and treatment planning could be performed. For daily repositioning of the animals, alignment of bony structures in native CT scans was well feasible. Fractionated irradiation caused a significant delay in tumor growth translating into significantly prolonged survival in clear dependence of the beam collimation setting and margin size. Brain sections revealed tumors of similar appearance and volume on the day of euthanasia. Importantly, the repeated contrast agent injections were well tolerated, as liver enzyme and creatinine serum levels were only subclinically elevated, and liver and kidney sections displayed normal histomorphology. Conclusions Contrast-enhanced, CT-based, fractionated radiation of orthotopic mouse GBM represents a versatile preclinical technique for the development and evaluation of multimodal radiotherapeutic approaches in combination with novel therapeutic agents in order to accelerate translation into clinical testing.
Related Links	https://ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-020-1470-2.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13014-020-1470-2
Journal	Radiation Oncology
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2020-01-22
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Radiotherapy Imaging Radiology Small animal tumor models Preclinical radiotherapy Molecular radiation oncology Orthotopic glioblastoma Samll animal radiotherapy Small animal radiation platforms
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Oncology
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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