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

Mol Imaging Biol. 2015 Aug;17(4):539-47. doi: 10.1007/s11307-014-0810-8.

Abstract

Purpose: We evaluated the dosimetry of [(89)Zr]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. [(89)Zr]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 [(89)Zr]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 [(89)Zr]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 [(64)Cu] rituximab (t½ = 12.7 h).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Lymphoma, B-Cell / diagnostic imaging*
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Phantoms, Imaging
  • Positron-Emission Tomography / methods*
  • Radioisotopes / analysis*
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / therapeutic use
  • Radiometry
  • Rituximab / therapeutic use*
  • Zirconium / analysis*
  • Zirconium / pharmacokinetics
  • Zirconium / therapeutic use

Substances

  • Antineoplastic Agents
  • Radioisotopes
  • Rituximab
  • Zirconium