Performance of (89)Zr-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 ((89)Zr)-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 (89)Zr-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 (89)Zr-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 (89)Zr-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 (89)Zr-rituximab on PET (SUV(peak) = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of (89)Zr-rituximab (range SUV(peak) = 3.2–5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of (89)Zr-rituximab was observed (SUV(peak) = 3.8), while the biopsy was CD20-negative. CONCLUSIONS: This study suggests a positive correlation between tumor uptake of (89)Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of (89)Zr-rituximab-PET as an imaging biomarker for CD20 targeting. For clinical application of (89)Zr-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.