Page 204 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 10
Tumor uptake of 89Zr-rituximab-PET was correlated to CD20 expression in biopsies
As mentioned in the introduction, treatment of patients with B cell non-Hodgkin lymphoma includes rituximab, an anti-CD20 mAb. Insufficient tumor targeting might cause therapy failure in relapsed/refractory disease. In Chapter 7, we investigated the performance of 89Zr-rituximab-PET for assessment of CD20 targeting. CD20 expression in tumor biopsies was assessed by immunohistochemistry (IHC) in six patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). 89Zr-rituximab-PET scans were acquired and tumor uptake was assessed for the corresponding tumor lesions.
Tumor uptake on 89Zr-immuno-PET was concordant with IHC in 5 patients: in one patient no tumor uptake was observed on immuno-PET with absence of CD20 expression in the tumor biopsy, in the other four patients tumor uptake was concordant with CD20-positive biopsies. Intense tumor uptake of 89Zr-rituximab on PET (SUVpeak=12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of 89Zr-rituximab (range SUVpeak = 3.2-5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of 89Zr-rituximab was observed (SUVpeak = 3.8), while the biopsy was CD20-negative, indicating either a false-positive immuno-PET finding or heterogeneous target expression/sampling error of the biopsy. Therefore, to understand the cause of this discordant finding further analysis of the imaging signal is required, as the total PET signal consists the sum of non-specific and target-mediated, specific uptake.
Overall, these results indicate the potential of 89Zr-rituximab-PET as an imaging biomarker for CD20 expression. Subsequently, the value of PET imaging with 89Zr-rituximab to predict response to therapy has to be determined.
89Zr-immuno-PET can be used to assess antigen-mediated uptake in normal tissues
Especially in early stages of drug development, it is of interest to identify which therapeutic mAb has high potential to provide selective treatment by targeting the tumor, without affecting normal tissues. A non-invasive technique to investigate and predict antigen-mediated uptake in normal tissues is expected to improve drug development strategies. Antigen-mediated, specific uptake is expected to be dose-dependent. If the target antigen is present on normal tissues, dose-dependent uptake is expected (this is also referred to as the antigen sink).
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