Relative biologic effects of low-dose-rate alpha-emitting 227Th-rituximab and beta-emitting 90Y-tiuexetan-ibritumomab versus external beam X-radiation

Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):186-92. doi: 10.1016/j.ijrobp.2008.05.029.


Purpose: To determine the relative biologic effects (RBE) of alpha-particle radiation from 227Th-rituximab and of beta-radiation from 90Y-tiuexetan-ibritumomab (Zevalin) compared with external beam X-radiation in the Raji lymphoma xenograft model.

Methods and materials: Radioimmunoconjugates were administered intravenously in nude mice with Raji lymphoma xenografts at different levels of activity. Absorbed dose to tumor was estimated by separate biodistribution experiments for 227Th-rituximab and Zevalin. Tumor growth was measured two to three times per week after injection or X-radiation. Treatment-induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm3, respectively, was used as an end point.

Results: The absorbed radiation dose-rate in tumor was slightly more than 0.1 Gy/d for the first week following injection of 227Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days after injection. For treatment with Zevalin the maximum dose-rate in tumor was achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01 Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for 227Th-rituximab and between 1 and 1.3 for Zevalin.

Conclusions: Both at low doses and low-dose-rates, the 227Th-rituximab treatment was more effective per absorbed radiation dose unit than the two other treatments. The considerable effect at low doses suggests that the best way to administer low-dose-rates, alpha-emitting radioimmunoconjugates is via multiple injections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha Particles / therapeutic use
  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Beta Particles / therapeutic use
  • Dose-Response Relationship, Radiation
  • Female
  • Half-Life
  • Immunoconjugates / pharmacokinetics
  • Immunoconjugates / therapeutic use*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / radiotherapy
  • Mice
  • Mice, Inbred C3H
  • Mice, Nude
  • Radioimmunotherapy / methods
  • Relative Biological Effectiveness*
  • Rituximab
  • Thorium / pharmacokinetics
  • Thorium / therapeutic use*
  • Transplantation, Heterologous
  • Yttrium Radioisotopes / pharmacokinetics
  • Yttrium Radioisotopes / therapeutic use*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoconjugates
  • Yttrium Radioisotopes
  • Rituximab
  • ibritumomab tiuxetan
  • Thorium