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2′-deoxy-2′-[18F] fluoro-D-glucose positron emission tomography, diffusion-weighted magnetic resonance imaging, and choline spectroscopy to predict the activity of cetuximab in tumor xenografts derived from patients with squamous cell carcinoma of the head and neck

Lionel Mignion, Sandra Schmitz, Nicolas Michoux, Xavier Caignet, Rose-Marie Goebbels, Anne Bol, Marie-Aline C. Neveu, Vincent Grégoire, Thierry Duprez, Renaud Lhommel, Fréderic Amant, Els Hermans, Benedicte F. Jordan and Jean-Pascal Machiels _

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Oncotarget. 2018; 9:28572-28585. https://doi.org/10.18632/oncotarget.25574

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Abstract

Lionel Mignion1, Sandra Schmitz2, Nicolas Michoux3, Xavier Caignet2, Rose-Marie Goebbels2, Anne Bol4, Marie-Aline C. Neveu1, Vincent Grégoire4, Thierry Duprez3, Renaud Lhommel5, Fréderic Amant6, Els Hermans6, Benedicte F. Jordan1 and Jean-Pascal Machiels2

1Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium

2Institut Roi Albert II, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale, Université catholique de Louvain, Brussels, Belgium

3Department of Radiology and Medical Imaging, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

4Center for Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium

5Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (POLE MIRO), Université Catholique de Louvain, Brussels, Belgium

6Department of Oncology, Gynecologic Oncology, KU Leuven (University of Leuven), Leuven, Belgium

Correspondence to:

Jean-Pascal Machiels, email: jean-pascal.machiels@uclouvain.be

Keywords: cetuximab; FDG-PET; DW-MRI; patient-derived tumor xenograft; head and neck cancer

Abbreviations: 18FDG-PET: 2′-deoxy-2′-[18F] fluoro-D-glucose positron emission tomography; DWI-MRI: diffusion-weighted magnetic resonance imaging; SCCHN: squamous cell carcinoma of the head and neck

Received: January 19, 2018     Accepted: May 19, 2018     Published: June 19, 2018

ABSTRACT

We investigated changes on 2′-deoxy-2′-[18F]fluoro-D-glucose positron emission tomography (18FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI), and choline spectroscopy as early markers of cetuximab activity in squamous cell carcinoma of the head and neck (SCCHN).

SCCHN patient-derived tumor xenografts models were selected based on their cetuximab sensitivity. Three models were resistant to cetuximab and two were sensitive (one was highly sensitive and the other one was moderately sensitive). Cetuximab was infused on day 0 and 7. Maximal standardized uptake values (SUVmax), apparent diffusion coefficient (ADC), and total choline pool were measured at baseline and at day 8. To investigate the possible clinical relevance of our pre-clinical findings, we also studied the SUVmax and ADC modifications induced by cetuximab in five patients.

Cetuximab induced a significant decrease in SUVmax and an increase in ADC at day 8 compared to baseline in the most cetuximab-sensitive model but not in the other models. At day 8, in one resistant model, SUVmax was decreased compared to baseline and was significantly lower than the controls. Choline spectroscopy was not able to predict cetuximab activity. The five patients treated with cetuximab had a 18FDG-PET partial response. One patient had a partial response according to RECISTv1.1. Interestingly, this last had also an increase in ADC value above 25%.

Our preclinical data support the use of PDTX to investigate imaging techniques to detect early treatment response. Our pre-clinical and clinical data suggest that DW-MRI and 18FDG-PET should be further investigated to predict cetuximab activity.


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