Translational Therapeutics

Does multiparametric imaging with 18F-FDG-PET/MRI capture spatial variation in immunohistochemical cancer biomarkers in head and neck squamous cell carcinoma?



The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy.


Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis.


Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy.


We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.

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Fig. 1: Illustration of the steps in the study from a patient with a tumour in the oral cavity and a lymph-node metastasis in level I.
Fig. 2: Example of multiparametric imaging with FDG uptake, diffusion and perfusion of a patient with a T2N0M0 tumour in the right maxilla involving both the maxillary sinus and the oral cavity.
Fig. 3: Boxplot illustrating the heterogeneity of vital tumour cells (VTC) and the IHC biomarkers in each of the 194 cores from all 33 lesions.
Fig. 4: Example of the functional imaging and pathology from a patient with a lymph node metastasis.


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The authors thank Katrin E. Håkansson, PhD, for her guidance in using the statistical software R.

Author information




J.H.R., I.V.R., S.M.B., I.W., C.v.B., L.S.P. and B.M.F. contributed substantially to the conception and the design of the study. J.H.R., A.O., G.L., A.E.H., F.L.A., H.H.J. and A.K. contributed substantially to the acquisition and analysis. J.H.R., I.V.R., S.M.B. and B.M.F contributed substantially to the analysis and all authors contributed to the interpretation as well as writing the paper. All authors have approved the paper.

Corresponding author

Correspondence to Jacob H. Rasmussen.

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Ethics approval and consent to participate

The study was approved by Regional Committee on Health Research Ethics (The Capital Region of Denmark), approval number H-16049387. All patients provided informed consent to participate in the study, and the study was conducted accordance with the Declaration of Helsinki.

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Not applicable.

Data availability

The data set used and analysed during the current study is available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding information

This project received funding from the Research Foundation of Rigshospitalet, the Danish Cancer Society (grant nos. R167-A10858 and R134-A8543-B79), the Aase and Ejnar foundation, National Cancer Institute (NCI grant no. P30 CA 134274-04) the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 670261), the Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, Svend Andersen Foundation, the Neye Foundation. SMB acknowledges support from the Maryland Department of Health’s Cigarette Restitution Fund Program and the NCI University of Maryland Cancer Center Support Grant (P30CA134274).

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Rasmussen, J.H., Olin, A., Lelkaitis, G. et al. Does multiparametric imaging with 18F-FDG-PET/MRI capture spatial variation in immunohistochemical cancer biomarkers in head and neck squamous cell carcinoma?. Br J Cancer 123, 46–53 (2020).

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