Page 202 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 10
trastuzumab-emtansine (T-DM1). In this study in patients with HER2-positive metastatic breast cancer, tumor detection and staging was performed with conventional imaging (18F-FDG-PET) and in addition, tumor targeting was assessed with 89Zr-trastuzumab-PET (6). After 3 cycles of treatment with trastuzumab-emtansine (T-DM1), early response was assessed with conventional imaging (18F-FDG-PET). This is a promising design for future application of 89Zr- immuno-PET as a clinical tool to guide antibody-based therapy.
“All that is gold does not glitter”
Based on this review of initial clinical trials with 89Zr-immuno-PET, further development of 89Zr-immuno-PET is required to allow assessment of target engagement. Two requirements for each 89Zr-labeled mAb were identified to realize its full potential. One requirement is that the biodistribution of the 89Zr- labeled mAb (imaging dose) reflects the biodistribution of the drug during treatment (therapeutic dose). Another requirement is that PET should be capable to assess the specific, antigen-mediated, tumor uptake of the 89Zr-MAb. Currently, there are no standardized criteria to define positive uptake on 89Zr-immuno-PET. This may be improved by quantitative analysis of tumor uptake on 89Zr-immuno- PET. Therefore, imaging procedures, including data analysis and quantitative measurements of tumor uptake should be standardized and validated for future application of 89Zr-immuno-PET.
Part II Validation of 89Zr-immuno-PET
For each new measurement instrument, knowledge of measurement variability is required for correct interpretation of the results. For 18F-FDG-PET, measurement variability for tumor uptake measured with SUV is approximately 10% (7). 89Zr- immuno-PET is challenged by the low injected dose and low positron abundance of 89Zr, leading to a relative low signal-to-noise ratio. These factors will result in increased measurement variability for 89Zr-immuno-PET compared to 18F-FDG- PET.
Therefore, we investigated two sources of measurement variability for 89Zr- immuno-PET: noise-induced variability (Chapter 5) and interobserver reproducibility of tumor uptake quantification (Chapter 6).
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