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Clinical & Experimental Metastasis

, Volume 34, Issue 1, pp 51–62 | Cite as

Use of non-invasive imaging to monitor response to aflibercept treatment in murine models of colorectal cancer liver metastases

  • Karianne G. Fleten
  • Kine M. Bakke
  • Gunhild M. Mælandsmo
  • Andreas Abildgaard
  • Kathrine Røe Redalen
  • Kjersti FlatmarkEmail author
Research Paper

Abstract

The liver is the most frequent metastatic site in colorectal cancer (CRC), and relevant orthotopic in vivo models are needed to study the efficacy of anticancer drugs in the metastatic setting. A challenge when utilizing such models is monitoring tumor growth during the experiments. In this study, experimental liver metastases were established in nude mice by splenic injection of the CRC cell lines HT29 and HCT116, and the mice were treated with the antiangiogenic drug aflibercept. Tumor growth was monitored using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). Aflibercept treatment was well tolerated and resulted in increased animal survival in HCT116, but not in HT29, while inhibited tumor growth was observed in both models. Treatment efficacy was monitored with high precision using MRI, while BLI detected small-volume disease with high sensitivity, but was less accurate in end-stage disease. Apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DW-MRI) were highly predictive of treatment response, with increased ADC corresponding well with areas of necrosis observed by histological evaluation of aflibercept-treated xenografts. The results showed that the efficacy of the antiangiogenic drug aflibercept varied between the two models, possibly reflecting unique growth patterns in the liver that may be representative of human disease. Non-invasive imaging, especially MRI and DW-MRI, can be used to effectively monitor tumor growth and treatment response in orthotopic liver metastasis models.

Keywords

Colorectal cancer Liver metastasis In vivo models Aflibercept Non-invasive imaging 

Abbreviations

ADC

Apparent diffusion coefficient

CRC

Colorectal cancer

BLI

Bioluminescence

DCE-MRI

Dynamic contrast enhanced MRI

DW-MRI

Diffusion weighted-MRI

ECG

Electrocardiography

FLASH

Fast low angle shot

GFP

Green fluorescent protein

MRI

Magnetic resonance imaging

RARE

Rapid acquisition with relaxation enhancement

SE

Spin echo

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

This work was kindly supported by the Norwegian Cancer Society (Grant No. [#42185263650] to KGF).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10585_2016_9829_MOESM1_ESM.pdf (336 kb)
Supplementary Table 1 An overview of the number of mice used in the different experiments with HCT116 and HT29 cells, number of mice censored, reasons for censoring and experimental details

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium HospitalOslo University HospitalOsloNorway
  2. 2.Faculty of MedicineUniversity of OsloOsloNorway
  3. 3.Department of OncologyAkershus University HospitalLørenskogNorway
  4. 4.Department of PhysicsUniversity of OsloOsloNorway
  5. 5.Department of PharmacyUniversity of TromsøTromsøNorway
  6. 6.Department of Radiology and Nuclear Medicine, RikshospitaletOslo University HospitalOsloNorway
  7. 7.Department of Gastroenterological Surgery, Norwegian Radium HospitalOslo University HospitalOsloNorway

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