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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.

plos one

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