Page 102 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Chapter 5
studies for non-oncological indications, e.g. rheumatoid arthritis and multiple sclerosis (5,6), as further limiting radiation exposure (to <10 mSv) is necessary for these patient categories.
Knowledge of measurement variability is of interest as a small measurement error is required for the detection of even small changes over time (e.g. response evaluation, within patients). In the current study, we assessed noise induced variability as source of measurement error (expressed as repeatability coefficient (RC) in %). For clinical relevance, assessment of reliability is important as this indicates the ability to divide patients in groups of interest despite measurement errors (e.g. response prediction, between patients). Therefore an explorative reliability analysis was performed (expressed as intraclass correlation coefficients (ICC)) reflecting the contribution of this source of measurement variability to the observed differences (total variance) in biodistribution and tumor uptake in these datasets.
Potential clinical applications of Zr-89-immuno-PET include use as a quantitative imaging biomarker to assess antibody uptake in normal tissue and tumor to guide individualized treatment and/or drug development (3).
MATERIALS AND METHODS
Data sources
Original list mode data were taken from three clinical 89Zr-immuno-PET studies: 89Zr-antiCD20 mAb in non-Hodgkin lymphoma (7), 89Zr-anti-epidermal growth factor receptor (EGFR) mAb in colorectal cancer (8), and 89Zr-antiCD44 mAb in solid tumors (9). The original injected dose was 74 MBq for 89Zr-antiCD20 mAb, 37 MBq for 89Zr-antiEGFR mAb and 37 MBq for 89Zr-antiCD44 mAb. Scans were scheduled at the following time points: 1, 72 and 144 h p.i. (D0, D3, D6) for 89Zr- antiCD20 mAb and 89Zr-antiEGFR mAb, and 1, 24 and 96 h p.i. (D0, D1, D4) for 89Zr-antiCD44 mAb. Study procedures, including image acquisition protocols, have been reported previously (7-9). All data were acquired on a Philips Gemini 64 or Ingenuity 128 PET/CT scanner (Philips Healthcare). The number of bed positions (for a scan trajectory of mid-thigh to vertex of the skull) was 10-12, with a 50% bed overlap. Data were acquired for 5 minutes per bed. Data were normalized, corrected for decay, randoms, dead time, scatter and attenuation and reconstructed using 3D BLOB-OS-TF (3 iterations, 33 subsets). A 7mm Gaussian post
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