Radiotoxicity of the Alpha-Emitting Bone-Seeker 223Ra Injected Intravenously Into Mice: Histology, Clinical Chemistry and Hematology

In Vivo. May-Jun 2006;20(3):325-31.

Abstract

Background: The alpha-emitter 223Ra, which localizes in osteoblastic active zones, including on skeletal surfaces and in osteoblastic metastases, has recently been introduced as a potential therapeutic agent against skeletal metastases. Here, the adverse effects of high dosages in animals were investigated.

Materials and methods: Balb/c mice received intravenously (i.v.) either 1250, 2500, or 3750 kBq/kg of dissolved 223RaCl2 and were followed in the initial toxicity phase. At the 4-week end-point, the animals were sacrificed and blood samples were collected to study the effects on clinical chemistry and hematological parameters. Selected organs were weighed and tissue samples examined by microscopy.

Results: Treatment with 223Ra caused a dose-related minimal to moderate depletion of osteocytes and osteoblasts in the bones. Furthermore, a dose-related minimal to marked depletion of the hematopoietic cells in the bone marrow, and a minimal to slight extramedullary hematopoiesis in the spleen and in the mandibular and mesenteric lymph nodes were observed. The LD50 for acute toxicity, defined as death within 4 weeks of receiving the substance, was not reached.

Conclusion: This study demonstrated that high doses of the bone-seeker 223Ra did not completely inactivate the blood-producing cells. The relatively high tolerance to skeletal alpha doses was probably caused by the surviving pockets of red bone marrow cells beyond the range of alpha particles from the bone surfaces, and the recruitment of peripheral stems cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha Particles / adverse effects*
  • Animals
  • Clinical Chemistry Tests
  • Dose-Response Relationship, Radiation
  • Female
  • Femur / diagnostic imaging
  • Femur / metabolism
  • Hematologic Tests
  • Hematopoiesis / radiation effects*
  • Histological Techniques
  • Injections, Intravenous
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Osteoclasts / radiation effects*
  • Osteocytes / radiation effects*
  • Radionuclide Imaging
  • Radium / administration & dosage
  • Radium / toxicity*
  • Spleen / diagnostic imaging
  • Spleen / metabolism
  • Sternum / diagnostic imaging
  • Sternum / metabolism
  • Time Factors

Substances

  • Radium