Page 144 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 7
ABSTRACT
Purpose: Treatment of patients with diffuse large B cell lymphoma (DLBCL) includes rituximab, an anti-CD20 monoclonal antibody (mAb). Insufficient tumor targeting might cause therapy failure. Tumor uptake of 89Zirconium (89Zr)-mAb is a potential imaging biomarker for tumor targeting, since it depends on target antigen expression and accessibility. The aim of this pilot study was to describe the performance of 89Zr-labeled-rituximab PET to assess CD20 targeting in patients with relapsed/refractory DLBCL.
Methods: Six patients with biopsy-proven DLBCLwere included. CD20 expression was assessed using immunohistochemistry (IHC). 74 MBq 89Zr-rituximab (10 mg) was administered after the therapeutic dose of rituximab. Immuno-PET scans on day 0, 3 and 6 post injection (D0, D3 and D6 respectively) were visually assessed and quantified for tumor uptake. Spearman’s rank correlation coefficient was used to assess the correlation between tumor uptake of 89Zr-rituximab and ranking of CD20 expression in biopsies.
Results: Tumor uptake of 89Zr-rituximab and CD20 expression were concordant in 5 patients: for one patient, both were negative, for the other four patients visible 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 with 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. Overall, a positive correlation was observed between tumor uptake of 89Zr-rituximab and CD20 expression in the biopsied tumor lesions (rs=0.83, p=0.04, n=6).
Conclusions: This study provides evidence for the use of 89Zr-rituximab-PET as an imaging biomarker to assess CD20 targeting, given the observed correlation between tumor uptake of 89Zr-rituximab and CD20 expression in biopsies. Therefore, 89Zr-rituximab-PET allows for further studies relating tumor targeting to clinical benefit of rituximab treatment in individual patients.
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