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

by Yvonne W. S. Jauw, Josée M. Zijlstra, Daphne de Jong, Danielle J. Vugts, Sonja Zweegman, Otto S. Hoekstra, Guus A. M. S. van Dongen, Marc C. Huisman

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 DLBCL were 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.

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 (SUV_peak = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of ⁸⁹Zr-rituximab (range SUV_peak = 3.2–5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of ⁸⁹Zr-rituximab was observed (SUV_peak = 3.8), while the biopsy was CD20-negative.

Conclusions

This study suggests a positive correlation between tumor uptake of ⁸⁹Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of ⁸⁹Zr-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.

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