PET imaging of zirconium-89 labelled cetuximab: A phase I trial in patients with head and neck and lung cancer

Judith van Loon*, Aniek J. G. Even, Hugo J. W. L. Aerts, Michel Ollers, Frank Hoebers, Wouter van Elmpt, Ludwig Dubois, Anne-Marie C. Dingemans, Roy I. Lalisang, Pascal Kempers, Boudewijn Brans, Veronique Winnepenninckx, Ernst-Jan Speel, Eric Thunnissen, Kim M. Smits, Ronald Boellaard, Danielle J. Vugts, Dirk De Ruysscher, Philippe Lambin

*Corresponding author for this work

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Abstract

Background and purpose: PET imaging of cetuximab uptake may help selecting cancer patients with the highest chance of benefit. The aim of this phase I trial was to determine the safety of the tracer (89)zr-cetuximab and to assess tumour uptake.

Methods: Two dose schedules were used; two consecutive doses of 60 MBq Zr-89-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m(2) of unlabelled cetuximab. Toxicity (CTCAE 3.0) was scored twice weekly. PET-CT scans were acquired on days 4, 5 and 6 (step 1) or 5, 6, 7 (step 2). Because tumour uptake could not be assessed satisfactorily, a third step was added including EGFR overexpressing tumours.

Results: Nine patients were included (6 NSCLC; 3 HNC). No additional toxicity was associated with administration of 89Zr-cetuximab compared to standard cetuximab. A tumour to blood ratio (TBR) > 1 was observed in all but one patient, with a maximum of 4.56. TBR was not different between dose schedules. There was a trend for higher TBR at intervals > 5 days after injection.

Conclusions: Both presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)267-273
Number of pages7
JournalRadiotherapy and Oncology
Volume122
Issue number2
DOIs
Publication statusPublished - Feb 2017

Keywords

  • Zr-89-cetuximab
  • EGFR
  • Immuno-PET
  • Phase I trial
  • GROWTH-FACTOR RECEPTOR
  • MONOCLONAL-ANTIBODIES
  • PLUS CETUXIMAB
  • 1ST-LINE CHEMOTHERAPY
  • EGFR-INHIBITION
  • IMMUNO-PET
  • EXPRESSION
  • RADIOTHERAPY
  • CARCINOMA
  • SURVIVAL

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