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).
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.
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.
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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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.
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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
- ImmunoPET tracer