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Molecular Imaging and Biology

, Volume 15, Issue 4, pp 468–475 | Cite as

Evaluation of 89Zr-rituximab Tracer by Cerenkov Luminescence Imaging and Correlation with PET in a Humanized Transgenic Mouse Model to Image NHL

  • Arutselvan Natarajan
  • Frezghi Habte
  • Hongguang Liu
  • Ataya Sathirachinda
  • Xiang Hu
  • Zhen Cheng
  • Claude M. Nagamine
  • Sanjiv Sam Gambhir
Research Article

Abstract

Purpose

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.

Procedures

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 (R 2 = 0.85 and slope = 0.576), which also confirmed the corresponding correlations parameter value (R 2 = 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.

Key words

Cerenkov radiation Immuno-CLI 89Zr-rituximab huCD20 imaging 

Notes

Acknowledgments

We acknowledge the support of the Small Animal Imaging Core, the Quantitation and Visualization Core, Reyhan Kader, Dr. Timothy Doyle, and the National Cancer Institute grant support ICMIC P50CA114747 (SSG). No other potential conflict of interest relevant to this article was reported.

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Copyright information

© World Molecular Imaging Society 2013

Authors and Affiliations

  • Arutselvan Natarajan
    • 1
  • Frezghi Habte
    • 1
  • Hongguang Liu
    • 1
  • Ataya Sathirachinda
    • 1
  • Xiang Hu
    • 1
  • Zhen Cheng
    • 1
  • Claude M. Nagamine
    • 2
  • Sanjiv Sam Gambhir
    • 1
    • 3
  1. 1.Molecular Imaging Program at Stanford (MIPS), Department of RadiologyStanford UniversityStanfordUSA
  2. 2.Department of Comparative MedicineStanford UniversityStanfordUSA
  3. 3.Bioengineering, Materials Science and EngineeringStanford UniversityStanfordUSA

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