title: Evaluation of 89Zr-rituximab tracer by Cerenkov luminescence imaging and correlation with PET in a humanized transgenic mouse model to image NHL.
abstract: OBJECTIVE
  This research aimed to study the use of Cerenkov luminescence imaging (CLI) for non-Hodgkin's lymphoma (NHL) using 89Zr-rituximab positron emission tomography (PET) tracer with a humanized transgenic mouse model that expresses human CD20 and the correlation of CLI with PET.
  
  
  METHODS
  Zr-rituximab (2.6 MBq) was tail vein-injected into transgenic mice that express the human CD20 on their B cells (huCD20TM). One group (n=3) received 2 mg/kg pre-dose (blocking) of cold rituximab 2 h prior to tracer; a second group (n=3) had no pre-dose (non-blocking). CLI was performed using a cooled charge-coupled device optical imager. We also performed PET imaging and ex vivo studies in order to confirm the in vivo CLI results. At each time point (4, 24, 48, 72, and 96 h), two groups of mice were imaged in vivo and ex vivo with CLI and PET, and at 96 h, organs were measured by gamma counter.
  
  
  RESULTS
  huCD20 transgenic mice injected with 89Zr-rituximab demonstrated a high-contrast CLI image compared to mice blocked with a cold dose. At various time points of 4-96 h post-radiotracer injection, the in vivo CLI signal intensity showed specific uptake in the spleen where B cells reside and, hence, the huCD20 biomarker is present at very high levels. The time-activity curve of dose decay-corrected CLI intensity and percent injected dose per gram of tissue of PET uptake in the spleen were increased over the time period (4-96 h). At 96 h, the 89Zr-rituximab uptake ratio (non-blocking vs blocking) counted (mean±standard deviation) for the spleen was 1.5±0.6 for CLI and 1.9±0.3 for PET. Furthermore, spleen uptake measurements (non-blocking and blocking of all time points) of CLI vs PET showed good correlation (R2=0.85 and slope=0.576), which also confirmed the corresponding correlations parameter value (R2=0.834 and slope=0.47) obtained for ex vivo measurements.
  
  
  CONCLUSIONS
  CLI and PET of huCD20 transgenic mice injected with 89Zr-rituximab demonstrated that the tracer was able to target huCD20-expressing B cells. The in vivo and ex vivo tracer uptake corresponding to the CLI radiance intensity from the spleen is in good agreement with PET. In this report, we have validated the use of CLI with PET for NHL imaging in huCD20TM.
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, James H. Clark Center, 318 Campus Drive, E153, Stanford, CA 94305, USA.
authors.forename: Arutselvan
authors.initials: A
authors.lastname: Natarajan
authors.forename: Frezghi
authors.initials: F
authors.lastname: Habte
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.forename: Ataya
authors.initials: A
authors.lastname: Sathirachinda
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.forename: Claude M
authors.initials: CM
authors.lastname: Nagamine
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D049449:Luminescence; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging*; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D000069283:Rituximab; D014018:Tissue Distribution
chemical_list: C586248:89Zr-rituximab; D058846:Antibodies, Monoclonal, Murine-Derived; D011849:Radioactive Tracers; D000069283:Rituximab