Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Yvonne W. S. Jauw*, Dennis F. Heijtel, Josee M. Zijlstra, Otto S. Hoekstra, Henrica C. W. de Vet, Danielle J. Vugts, Henk M. Verheul, Ronald Boellaard, Sonja Zweegman, Guus A. M. S. van Dongen, C. Willemien Menke-van der Houven van Oordt, Adriaan A. Lammertsma, Marc C. Huisman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

PurposePositron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.ProceduresData were acquired from three previously reported clinical studies with [Zr-89]antiCD20 (74MBq, n=7), [Zr-89]antiEGFR (37MBq, n=7), and [Zr-89]antiCD44 (37MBq, n=13), with imaging obtained 1 to 6days post injection (D0-D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50% of the original injected dose (e.g., 37MBq(74inj)).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.ResultsThe RC for the combined manually delineated organs for [Zr-89] antiCD20 (37 MBq(74inj)) increased from D0 to D6 and was less than 6% at all time points. Blood pool and bone marrow had higher RC, up to 43% for 37 MBq(74inj) at D6. For tumor, the RC was up to 42% for [Zr-89]antiCD20 (37 MBq(74inj)). For [Zr-89]antiCD20, (18 MBq(74inj)), [Zr-89]antiEGFR (18 MBq(37inj)), and [Zr-89]antiCD44 (18 MBq(37inj)), measurement variability was independent of the investigated antibody.ConclusionsBased on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37MBq) around 6% for manually delineated organs combined, increasing up to 43% at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42%.

Original languageEnglish
Pages (from-to)1025-1034
Number of pages10
JournalMolecular Imaging and Biology
Volume20
Issue number6
DOIs
Publication statusPublished - Dec-2018

Keywords

  • Molecular imaging
  • Positron emission tomography
  • Zirconium-89
  • Immuno-PET
  • Monoclonal antibodies
  • POSITRON-EMISSION-TOMOGRAPHY
  • CELL LUNG-CANCER
  • F-18-FDG PET
  • MONOCLONAL-ANTIBODIES
  • REPEATABILITY

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