Page 114 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 5
This study provides the first description of noise induced variability for Zr- 89-immuno-PET. In literature more sophisticated applications of the technique of count reduced images have been described (23,24). By using bootstrapping the difference between the two image estimates can be obtained more precisely, which would allow for an examination of the change of noise induced variability with patient specific factors such as tumor size, uptake, patient size and location of the tumor in the patient. In addition, through application of this technique, the effect of lowering the injected dose on quantitative accuracy can be assessed.
Our results suggest that, as expected, measurement error may be dependent on volume and uptake (Supplemental Figure 1). In future work, phantoms could be used to study dependencies of noise induced variability on e.g. VOI volume and activity concentration. Such phantom experiments could be combined with tumor characteristics as derived from clinical Zr-89-immuno-PET studies (tumor volume, SUV, tumor to background ratio and localization) to obtain a detection limit for tumor identification. The trade-off between noise and contrast will determine the optimal time point for tumor imaging. In addition, tumor contrast on clinical images should be defined and characterized, allowing for a recommendation on the optimal time points for future clinical studies.
For potential application of immuno-PET with Zr-89-labeled antibodies as a quantitative imaging biomarker to predict which patients are likely to respond to antibody treatment, the ability to distinguish biological differences in antibody uptake between patients is required. We observed excellent ICCs (lesion based analysis), suggesting that an injected dose of 18-37MBq was sufficient for the datasets included. In general, justification of the injected dose should be based on the expected effect size in the population of interest.
Another clinical application of Zr-89-immuno-PET is in-vivo quantification of antibody biodistribution and tumor uptake to assess novel antibodies during early phases of drug development. For this purpose, noise induced variability as source of measurement error as reported in our study (expressed as RC) can be applied to estimate the minimal measurement variability (e.g. for sample size calculations for novel studies).
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