Myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186rhenium-(tin)1,1- hydroxyethylidene diphosphonate (186Re-HEDP)

Cancer Biother Radiopharm. 2003 Dec;18(6):887-93. doi: 10.1089/108497803322702851.

Abstract

The aim of this study is to investigate the myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186Rhenium-(tin)1,1-hydroxyethylidene diphosphonate (186Re-HEDP) and to analyze the impact of amifostine on the bone uptake of the radiopharmaceutical. All animals were treated with 1000 MBq 186Re-HEDP. Group ReA received 500 mg amifostine prior to radionuclide therapy, group ReA3 received 3 x 200 mg amifostine 24 hours and 30 minutes prior to and 24 hours after radionuclide therapy. Group ReC served as control receiving no amifostine. Scintigrams were acquired to quantify the skeletal uptake of 186Re-HEDP, and platelet and leucocyte counts were measured. The mean decrease in platelets was 36% +/- 2%, 37% +/- 3%, and 61% +/- 5% for ReA, ReA3, and ReC, respectively. The decrease in ReC was significantly higher than in amifostine-treated animals with no difference between ReA and ReA3. For the leucocytes the mean decrease was 75% +/- 12%, 82% +/- 5%, and 73% +/- 4%, with no significant differences between the respective groups. Bone uptake of 186Re-HEDP was significantly reduced by 50% in ReA and ReA3 compared to ReC. Thus, the 3-day amifostine regimen had no advantage over the single dose regimen, with both regimens reducing bone uptake and yielding a platelet-protective but no leucoprotective effect.

Publication types

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

MeSH terms

  • Amifostine / administration & dosage
  • Amifostine / pharmacokinetics*
  • Animals
  • Blood Platelets / radiation effects
  • Bone Marrow / drug effects*
  • Bone Marrow / physiology*
  • Bone Marrow / radiation effects
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Drug Administration Schedule
  • Etidronic Acid / pharmacology
  • Etidronic Acid / therapeutic use*
  • Female
  • Infusions, Intravenous
  • Injections, Intravenous
  • Leukocytes / radiation effects
  • Organometallic Compounds / pharmacology
  • Organometallic Compounds / therapeutic use*
  • Rabbits
  • Radiation-Protective Agents / administration & dosage
  • Radiation-Protective Agents / pharmacokinetics*
  • Radionuclide Imaging / methods
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Time Factors

Substances

  • Organometallic Compounds
  • Radiation-Protective Agents
  • Radiopharmaceuticals
  • rhenium-186(tin)etidronate
  • Etidronic Acid
  • Amifostine