Performance of 89Zr-Labeled-Rituximab-PET as an Imaging Biomarker to Assess CD20 Targeting: A Pilot Study in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma

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 (89)Zirconium (Zr-89)-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 Zr-89-labeled-rituximab-PET to assess CD20 targeting in patients with relapsed/refractory DLBCL. Methods Six patients with biopsy-proven DLBCL were included. CD20 expression was assessed using immunohistochemistry (IHC). 74 MBq Zr-89-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. Results Tumor uptake of Zr-89-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 Zr-89-rituximab on PET (SUVpeak = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of Zr-89-rituximab (range SUVpeak = 3.2-5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of Zr-89-rituximab was observed (SUVpeak = 3.8), while the biopsy was CD20-negative. Conclusions This study suggests a positive correlation between tumor uptake of Zr-89-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of Zr-89-rituximab-PET as an imaging biomarker for CD20 targeting. For clinical application of 89Zr-rituximab-PET to guide individualized treatment, further studies are required to assess whether tumor targeting is related to clinical benefit of rituximab treatment in individual patients.