Positron emission tomography of 64Cu-DOTA-Rituximab in a transgenic mouse model expressing human CD20 for clinical translation to image NHL

Mol Imaging Biol. 2012 Oct;14(5):608-16. doi: 10.1007/s11307-011-0537-8.

Abstract

Purpose: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.

Procedures: (64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.

Results: PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.

Conclusions: PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal, Murine-Derived*
  • Antigens, CD20 / metabolism*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Copper Radioisotopes*
  • Dose-Response Relationship, Radiation
  • Heterocyclic Compounds, 1-Ring*
  • Humans
  • Isotope Labeling
  • Lymphoma, Non-Hodgkin / diagnostic imaging*
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Organometallic Compounds*
  • Positron-Emission Tomography / methods*
  • Tomography, X-Ray Computed
  • Translational Medical Research*

Substances

  • 64Cu-DOTA-rituximab
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Copper Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Organometallic Compounds
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid