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01-04-2016 | Research Article

The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [¹⁸ F]FDG/[¹⁸ F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model

Authors: Valerie S. Honndorf, Holger Schmidt, Stefan Wiehr, Hans F. Wehrl, Leticia Quintanilla-Martinez, Anke Stahlschmidt, Hervé Barjat, Sally-Ann Emmas, Bernd J. Pichler

Published in: Molecular Imaging and Biology | Issue 2/2016

Abstract

Purpose

Positron emission tomography (PET) and diffusion-weighted MRI (DW-MRI) were used to characterize the treatment effects of the MEK1/2 inhibitor selumetinib (AZD6244), docetaxel, and their combination in HCT116 tumor-bearing mice on the molecular level.

Procedures

Mice were treated with vehicle, selumetinib (25 mg/kg), docetaxel (15 mg/kg), or a combination of both drugs for 7 days and imaged at four time points with 2-deoxy-2-[¹⁸ F]fluoro-D-glucose ([¹⁸ F]FDG) or 3′-deoxy-3′-[¹⁸ F]fluorothymidine ([¹⁸ F]FLT) followed by DW-MRI to calculate the apparent diffusion coefficient (ADC). Data was cross-validated using the Pearson correlation coefficient (PCC) and compared to histology (IHC).

Results

Each drug led to tumor growth inhibition but their combination resulted in regression. Separate analysis of PET or ADC could not provide significant differences between groups. Only PCC combined with IHC analysis revealed the highest therapeutic impact for combination therapy.

Conclusion

Combination treatment of selumetinib/docetaxel was superior to the respective mono-therapies shown by PCC of PET and ADC in conjunction with histology.

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Title: The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [18 F]FDG/[18 F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model
Authors: Valerie S. Honndorf
Holger Schmidt
Stefan Wiehr
Hans F. Wehrl
Leticia Quintanilla-Martinez
Anke Stahlschmidt
Hervé Barjat
Sally-Ann Emmas
Bernd J. Pichler
Publication date: 01-04-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-015-0881-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [¹⁸ F]FDG/[¹⁸ F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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