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Radiation Dosimetry Study of [89Zr]rituximab Tracer for Clinical Translation of B cell NHL Imaging using Positron Emission Tomography

Abstract

Purpose

We evaluated the dosimetry of [89Zr]rituximab, an anti-CD20 immunoPET tracer to image B cell non-Hodgkin’s lymphoma (NHL) using a humanized transgenic mouse model that expresses human CD20 transgenic mice (huCD20TM).

Procedures

Rituximab was conjugated to desferrioxamine (Df) for radiolabeling of Zirconium-89. [89Zr]rituximab (2.8 ± 0.2 MBq) was tail vein-injected into huCD20T mice. Positron emission tomography (PET)/CT imaging was performed on the two groups of mice (blocking = 2 mg/kg pre-dose of rituximab and non-blocking; n = 5) at eight time points (1, 4, 24, 48, 72, 96, 120, and 168 h) post injection.

Results

The novel [89Zr]rituximab PET tracer had good immunoreactivity, was stable in human serum, and was able to specifically target human CD20 in mice. The human equivalents of highest dose (mean ± SD) organs with and without pre-dose are liver (345 ± 284 μSv/MBq) and spleen (1165 ± 149 μSv/MBq), respectively.

Conclusions

Dosimetry of the human patient whole-body dose was found to be 145 MBq per annum, and the patient dose-limiting organ will be the liver (with rituximab pre-dose blocking) and spleen for non-blocking. The [89Zr]rituximab (t½ = 78.4 h) imaging of B cell NHL patients could permit the observation of targeting lesions in NHL patients over an extended period due to longer half-life as compared to the [64Cu] rituximab (t½ = 12.7 h).

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Acknowledgments

We acknowledge the support of Ataya Sathirachinda, Drs. Timothy Doyle, Fred Chen, and Frezghi Habte, and the National Cancer Institute grant support ICMIC P50CA114747 (SSG). MicroPET/CT imaging and Gamma Counter measurements were performed in the SCi3 Stanford Small Animal Imaging Service Center.

Conflicts of Interest

The authors state they have no conflicts of interest

Author information

Correspondence to Sanjiv Sam Gambhir.

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Natarajan, A., Gambhir, S.S. Radiation Dosimetry Study of [89Zr]rituximab Tracer for Clinical Translation of B cell NHL Imaging using Positron Emission Tomography. Mol Imaging Biol 17, 539–547 (2015). https://doi.org/10.1007/s11307-014-0810-8

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Key words

  • Dosimetry
  • ImmunoPET tracer
  • [89Zr]rituximab
  • NHL