Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach
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Aniek J.G. Even1,*, Olga Hamming-Vrieze2,*, Wouter van Elmpt1, Véronique J.L. Winnepenninckx4, Jolien Heukelom2, Margot E.T. Tesselaar5, Wouter V. Vogel2,3, Ann Hoeben6, Catharina M.L. Zegers1, Daniëlle J. Vugts7, Guus A.M.S. van Dongen7, Harry Bartelink2, Felix M. Mottaghy8,9, Frank Hoebers1 and Philippe Lambin1
1 Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
2 Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
3 Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
4 Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands
5 Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
6 Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
7 Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands
8 Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
9 Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Aachen, Germany
* These authors have contributed equally to this work
Aniek J.G. Even, email:
Keywords: immuno-PET, Zirconium-89, cetuximab, LAHNSCC, EGFR
Received: November 30, 2016 Accepted: December 02, 2016 Published: December 11, 2016
Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.
Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.
Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).
In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.
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