Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach

Aniek J. G. Even*, Olga Hamming-Vrieze, Wouter van Elmpt, Veronique J. L. Winnepenninckx, Jolien Heukelom, Margot E. T. Tesselaar, Wouter V. Vogel, Ann Hoeben, Catharina M. L. Zegers, Danielle J. Vugts, Guus A. M. S. van Dongen, Harry Bartelink, Felix M. Mottaghy, Frank Hoebers, Philippe Lambin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 Zr-89-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 Zr-89-cetuximab varied between patients (day 6-7: SUVpeak range 2.56.2). 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, Zr-89-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.

Original languageEnglish
Pages (from-to)3870-3880
Number of pages11
JournalOncotarget
Volume8
Issue number3
DOIs
Publication statusPublished - 17 Jan 2017

Keywords

  • immuno-PET
  • Zirconium-89
  • cetuximab
  • LAHNSCC
  • EGFR
  • GROWTH-FACTOR RECEPTOR
  • CELL LUNG-CANCER
  • EGFR EXPRESSION
  • MACH-NC
  • CHEMOTHERAPY
  • SURVIVAL
  • RADIOTHERAPY
  • ZR-89
  • IMMUNOHISTOCHEMISTRY
  • METAANALYSIS

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