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Journal of Translational Medicine

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Open Access 01-12-2021 | Magnetic Resonance Imaging | Research

Feasibility and utility of MRI and dynamic ¹⁸F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer

Authors: Heidi Espedal, Hege F. Berg, Tina Fonnes, Kristine E. Fasmer, Camilla Krakstad, Ingfrid S. Haldorsen

Published in: Journal of Translational Medicine | Issue 1/2021

Abstract

Background

Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibility and utility of MRI and dynamic ¹⁸F-fluorodeoxyglucose (FDG)-PET imaging for monitoring tumor progression and assessing chemotherapy response in an orthotopic organoid-based patient-derived xenograft (O-PDX) mouse model of EC.

Methods

18 O-PDX mice (grade 3 endometrioid EC, stage IIIC1), selectively underwent weekly T2-weighted MRI (total scans = 32), diffusion-weighted MRI (DWI) (total scans = 9) and dynamic ¹⁸F-FDG-PET (total scans = 26) during tumor progression. MRI tumor volumes (vMRI), tumor apparent diffusion coefficient values (ADC_mean) and metabolic tumor parameters from ¹⁸F-FDG-PET including maximum and mean standard uptake values (SUV_max/SUV_mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of ¹⁸F-FDG (MR_FDG) were calculated. Further, nine mice were included in a chemotherapy treatment study (treatment; n = 5, controls; n = 4) and tumor ADC_mean-values were compared to changes in vMRI and cellular density from histology at endpoint. A Mann–Whitney test was used to evaluate differences between groups.

Results

Tumors with large tumor volumes (vMRI) had higher metabolic activity (MTV and TLG) in a clear linear relationship (r² = 0.92 and 0.89, respectively). Non-invasive calculation of MR_FDG from dynamic ¹⁸F-FDG-PET (mean MR_FDG = 0.39 μmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADC_mean (p = 0.03), lower vMRI (p = 0.03) and tumor cellular density (p = 0.02) than non-treated mice, all indicating treatment response.

Conclusion

Preclinical imaging mirroring clinical imaging methods in EC is highly feasible for monitoring tumor progression and treatment response in the present orthotopic organoid mouse model.

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Title: Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer
Authors: Heidi Espedal
Hege F. Berg
Tina Fonnes
Kristine E. Fasmer
Camilla Krakstad
Ingfrid S. Haldorsen
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Positron Emission Tomography
Endometrial Cancer
Endometrial Cancer
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-03086-9

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