Interobserver reproducibility of tumor uptake quantification with Zr-89-immuno-PET: a multicenter analysis

Yvonne W. S. Jauw*, Frederike Bensch, Adrienne H. Brouwers, Otto S. Hoekstra, Josee M. Zijlstra, Simone Pieplenbosch, Carolien P. Schröder, Sonja Zweegman, Guus A. M. S. van Dongen, C. Willemien Menke-van der Houven van Oordt, Elisabeth G. E. de Vries, Henrica C. W. de Vet, Ronald Boellaard, Marc C. Huisman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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PURPOSE: In-vivo quantification of tumor uptake of 89-zirconium (89Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for 89Zr-immuno-PET is low tumor contrast. This is expected to result in interobserver variation in tumor delineation. Therefore, the aim of this study was to determine interobserver reproducibility of tumor uptake measures by tumor delineation on 89Zr-immuno-PET scans.

METHODS: Data were obtained from previously published clinical studies performed with 89Zr-rituximab, 89Zr-cetuximab and 89Zr-trastuzumab. Tumor lesions on 89Zr-immuno-PET were identified as focal uptake exceeding local background by a nuclear medicine physician. Three observers independently manually delineated volumes of interest (VOI). Maximum, peak and mean standardized uptake values (SUVmax, SUVpeak and SUVmean) were used to quantify tumor uptake. Interobserver variability was expressed as the coefficient of variation (CoV). The performance of semi-automatic VOI delineation using 50% of background-corrected ACpeak was described.

RESULTS: In total, 103 VOI were delineated (3-6 days post injection (D3-D6)). Tumor uptake (median, interquartile range) was 9.2 (5.2-12.6), 6.9 (4.0-9.6) and 5.5 (3.3-7.8) for SUVmax, SUVpeak and SUVmean. Interobserver variability was 0% (0-12), 0% (0-2) and 7% (5-14), respectively (n = 103). The success rate of the semi-automatic method was 45%. Inclusion of background was the main reason for failure of semi-automatic VOI.

CONCLUSIONS: This study shows that interobserver reproducibility of tumor uptake quantification on 89Zr-immuno-PET was excellent for SUVmax and SUVpeak using a standardized manual procedure for tumor segmentation. Semi-automatic delineation was not robust due to limited tumor contrast.

Original languageEnglish
Pages (from-to)1840-1849
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number9
Publication statusPublished - Aug-2019


  • Adult
  • Aged
  • Antibodies, Monoclonal/metabolism
  • Biological Transport
  • Female
  • Humans
  • Lymphoma, B-Cell/diagnostic imaging
  • Male
  • Middle Aged
  • Observer Variation
  • Positron-Emission Tomography
  • Radioisotopes
  • Retrospective Studies
  • Zirconium

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