Page 113 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Noise-induced variability of 89Zr-immuno-PET
this reliability assessment (equation 2). Factors affecting [18F]-FDG-PET quantification have been described previously (15). Repeatability assessed by a classical test-retest study contains intra-patient variability between the test and the retest scan as well. For a test-retest study with Zr-89-immuno-PET, the following factors are expected to play a role 1) biological factors: e.g. uptake period (higher uptake levels at increasing time interval between injection and start of PET study), estimated at 1% for ± 1h (16,17); 2) physical factors: VOI definition, estimated at <1% for max and peak AC to 8% for mean (18). Based on the results of our study, we expect that noise induced variability will be a major contribution to measurement variability in a Zr-89-immuno-PET test-retest study (3% for large organs, 20% for tumor, values presented as SD instead of RC for comparison).
In previously reported test-retest studies of repeatability of 18F-FDG-PET,
RC of <10% have been reported for tumor uptake on 18F-FDG-PET, resulting in
thresholds of 10-15% needed to detect therapy-induced changes in patients with 5 non-small cell lung cancer [19-21]. For Zr-89-immuno-PET (37 MBq74inj), we
obtained similar RC of less than 10% for mean activity concentrations of manually
delineated organs. However, for tumor uptake on Zr-89-immuno-PET, RC up to
42% for SUVmax reflect the much lower signal to noise ratio in Zr-89-immuno-PET
scans in comparison to [18F]-FDG-PET scans. When immuno-PET with Zr-89-
labeled mAbs is used to assess response to treatment (e.g. by alteration of antigen
expression (22)), knowledge on measurement variability should be applied to set corresponding thresholds, following the example of the use of thresholds for
response assessment with [18F]-FDG-PET. For data already obtained, RC from our
study are relevant to allow correct interpretation, as differences smaller than the measurement variability cannot be attributed to biological effects. Measurement
variability (given as RC) is independent of the study population. In addition, RC
of tumor and blood pool are of interest when selecting an appropriate uptake
measure and/or VOI delineation method.
Tumor-to-blood ratios, which are commonly used, will result in even worse RC due to propagation of the individual RC as both numerator and denominator contain measurement variability. Future work may include an investigation to optimize delineation methods for image-derived blood pool (e.g. delineation of a larger region in the left ventricular cavity compared to a smaller fixed-size VOI in the aortic arch) to reduce noise induced variability. We designed this study based on patient data to provide a clinically relevant assessment of measurement error.
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