Page 153 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

DISCUSSION
Therapy failure in patients with relapsed/refractory DLBCL may be caused by insufficient CD20-mediated tumor targeting of rituximab. To elucidate the role of tumor targeting, development of an imaging biomarker to assess tumor targeting of rituximab is needed.
To our knowledge, this is the first study to report the performance of 89Zr- rituximab-PET as an imaging biomarker for CD20 targeting by correlating tumor uptake of 89Zr-rituximab as defined with PET and CD20 expression in biopsied tumor lesions. Tumor biopsies were obtained as routine work-up and tumor uptake on immuno-PET was evaluated at the biopsy sites. Overall, a positive correlation between tumor uptake of 89Zr-rituximab and CD20 expression in biopsies was observed.
In one patient, tumor uptake of 89Zr-rituximab was discordant with a CD20-negative biopsy. A possible explanation for the discrepancy is that the
tumor site was biopsied in a 18F-FDG-PET positive, 89Zr-rituximab-PET negative
part. IHC is the current gold standard for determination of CD20 expression,
however heterogeneity in target expression within and between tumor lesions may
not be detected by a single biopsy. Practical limitations of tumor biopsies are the invasiveness of the procedure and the fact that the tumor is not always safely 7 accessible.
Tumor uptake was quantified in regions with focal uptake exceeding local background. SUVpeak is commonly used as a measure of tumor uptake, but reflects only the highest uptake in a small part of the tumor. Manual delineation aims to capture total tumor uptake of 89Zr-rituximab, and allows for the derivation of SUVmean, its standard deviation and VOI volume. In this study the ranking of PET uptake was identical for SUVpeak and SUVmean. For 18F-FDG-PET in lymphoma, the Deauville criteria are used to define tumor uptake using liver and mediastinal blood pool as reference region (15). The observed tumor to blood ratios in this study (range 0.8-4.7) indicate a difference in an uptake criterion based on local contrast versus bloodpool as reference region. To develop a clinically relevant criterion for positive tumor uptake of 89Zr-rituximab further studies are required, linking tumor uptake to clinical outcome to rituximab treatment.
A limitation of our study is that the amount of circulating CD20+ B cells, which could influence tracer availability for tumor targeting, was not measured. However, tracer availability in the blood pool could be derived accurately from the
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