title: 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.
abstract: OBJECTIVE
  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 (SUVpeak = 12.8) corresponded with uniformly positive CD20 expression on IHC 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.
  
  
  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.
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvonne W S
authors.initials: YW
authors.lastname: Jauw
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Josée M
authors.initials: JM
authors.lastname: Zijlstra
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Vugts
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D012008:Recurrence; D015203:Reproducibility of Results; D000069283:Rituximab; D055815:Young Adult
chemical_list: C586248:89Zr-rituximab; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab