Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology

Hoelsken A, Schwarz M, Gillmann C, Pfister C, Uder M, Dörfler A, Buchfelder M, Schlaffer SM, Fahlbusch R, Buslei R, Bäuerle T (2018)

Publication Type: Journal article

Publication year: 2018

Journal

PLoS ONE Public Library of Science

Book Volume: 13

Journal Issue: 5

DOI: 10.1371/journal.pone.0197895

Abstract

PURPOSE: Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). METHODS: In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. RESULTS: Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. CONCLUSIONS: MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

Authors with CRIS profile

Clarissa Gillmann Institute of Radiology Michael Uder Lehrstuhl für Diagnostische Radiologie Arnd Dörfler Department of Neuroradiology Michael Buchfelder Lehrstuhl für Neurochirurgie Sven-Martin Schlaffer Lehrstuhl für Neurochirurgie Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung

Involved external institutions

Sozialstiftung Bamberg DE Germany (DE) International Neuroscience Institute GmbH (INI) DE Germany (DE)

How to cite

APA:

Hoelsken, A., Schwarz, M., Gillmann, C., Pfister, C., Uder, M., Dörfler, A.,... Bäuerle, T. (2018). Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology. PLoS ONE, 13(5). https://dx.doi.org/10.1371/journal.pone.0197895

MLA:

Hoelsken, Annett, et al. "Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology." PLoS ONE 13.5 (2018).

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