Oncotarget

Research Papers:

In vivo imaging of therapy response to a novel Pan-HER antibody mixture using FDG and FLT positron emission tomography

Carsten H. Nielsen, Mette M. Jensen, Lotte K. Kristensen, Anna Dahlman, Camilla Fröhlich, Helle J. Jacobsen, Thomas T. Poulsen, Johan Lantto, Ivan D. Horak, Michael Kragh and Andreas Kjaer _

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Oncotarget. 2015; 6:37486-37499. https://doi.org/10.18632/oncotarget.6060

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Abstract

Carsten H. Nielsen1,2,*, Mette M. Jensen1,2,*, Lotte K. Kristensen1,2, Anna Dahlman3, Camilla Fröhlich3, Helle J. Jacobsen3, Thomas T. Poulsen3, Johan Lantto3, Ivan D. Horak3, Michael Kragh3 and Andreas Kjaer1,2

1 Minerva Imaging ApS, Copenhagen, Denmark

2 Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

3 Symphogen A/S, Ballerup, Denmark

* These authors have contributed equally to this work

Correspondence to:

Andreas Kjaer, email:

Keywords: PET/CT, FDG and FLT, HER family, antibody therapy, pancreatic cancer

Received: July 28, 2015 Accepted: September 24, 2015 Published: October 09, 2015

Abstract

Purpose: Overexpression of the human epidermal growth factor receptor (HER) family and their ligands plays an important role in many cancers. Targeting multiple members of the HER family simultaneously may increase the therapeutic efficacy. Here, we report the ability to image the therapeutic response obtained by targeting HER family members individually or simultaneously using the novel monoclonal antibody (mAb) mixture Pan-HER.

Experimental design and results: Mice with subcutaneous BxPC-3 pancreatic adenocarcinomas were divided into five groups receiving vehicle or mAb mixtures directed against either EGFR (HER1), HER2, HER3 or all three receptors combined by Pan-HER. Small animal positron emission tomography/computed tomography (PET/CT) with 2’-deoxy-2’-[18F]fluoro-D-glucose (FDG) and 3’-deoxy-3’-[18F]fluorothymidine (FLT) was performed at baseline and at day 1 or 2 after initiation of therapy. Changes in tumor uptake of tracers were quantified and compared to reduction in tumor size. Imaging results were further validated by immunohistochemistry and qPCR. Mean FDG and FLT uptake in the Pan-HER treated group decreased by 19±4.3% and 24±3.1%, respectively. The early change in FDG and FLT uptake correlated with tumor growth at day 23 relative to day 0. Ex vivo molecular analyses of markers associated with the mechanisms of FDG and FLT uptake confirmed the in vivo imaging results.

Conclusions: Taken together, the study supports the use of FDG and FLT as imaging biomarkers of early response to Pan-HER therapy. FDG and FLT PET/CT imaging should be considered as imaging biomarkers in clinical evaluation of the Pan-HER mAb mixture.


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