title: High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model.
abstract: The aim of this experimental study was to investigate the myeloprotective potential of amifostine in rabbits receiving high-dose treatment with either (153)Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or (186)Re-hydroxyethylidene diphosphonate (HEDP) and to check for drug interactions impairing the skeletal uptake of these radiopharmaceuticals by amifostine.
  
  
  METHODS
  To a total of 24 rabbits, we administered 1,000 MBq of either (153)Sm-EDTMP (n = 12) or (186)Re-HEDP (n = 12). Six animals of each group received 500 mg amifostine intravenously 10-15 min before injection of the radiopharmaceutical, whereas the other 6 animals served as controls. Up to 8 wk after treatment, blood samples were collected every 3-5 d to measure platelet and leukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h, and 24 h after injection of the radiopharmaceutical to quantify the skeletal uptake.
  
  
  RESULTS
  For (186)Re-HEDP, the mean decrease in platelets was significantly less in the amifostine group (35.5% +/- 2.4%) than in the control group (61.3% +/- 5.4%, P < 0.001). Similar results were found for (153)Sm-EDTMP (36.5% +/- 8.3% vs. 52.3% +/- 14.0%, P < 0.05). No significant differences in leukocyte counts were found for (186)Re-HEDP (75.3% +/- 12.3% in the amifostine group and 72.5% +/- 4.1% in the control group, P > 0.05), whereas rabbits treated with (153)Sm-EDTMP plus amifostine showed a significantly greater decrease in leukocytes (69.2% +/- 10.8%) than did the control group (56.6% +/- 4.0%, P < 0.05). Bone uptake in percentage of initial total whole-body activity was significantly decreased in animals treated with amifostine compared with the control groups for both (186)Re-HEDP (15.8% +/- 3.1% vs. 30.9% +/- 1.9%, P < 0.001) and (153)Sm-EDTMP (31.7% +/- 8.9% vs. 44.0% +/- 6.5%, P < 0.05).
  
  
  CONCLUSIONS
  For amifostine, we found a highly significant cytoprotective effect on platelets but no leukoprotective effect. The latter probably relies on the intrinsic myelotoxicity of high-dose amifostine, which seemed to potentiate the leukodepression of the radiopharmaceuticals. The lower bone uptake in amifostine-treated animals may be caused by the chemical structure of amifostine, which is a potentially complex-forming compound that may be able to displace bisphosphonates from the rhenium- and samarium-bisphosphonate complexes, resulting in altered biodistribution patterns.
authors.affiliation: Clinic of Nuclear Medicine, Christian-Albrechts-Universität, Arnold-Heller-Strasse 9, D-24105 Kiel, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Brenner
authors.forename: W U
authors.initials: WU
authors.lastname: Kampen
authors.forename: C
authors.initials: C
authors.lastname: von Forstner
authors.forename: C
authors.initials: C
authors.lastname: Brümmer
authors.forename: M
authors.initials: M
authors.lastname: Zuhayra
authors.forename: C
authors.initials: C
authors.lastname: Muhle
authors.forename: N
authors.initials: N
authors.lastname: Czech
authors.forename: E
authors.initials: E
authors.lastname: Henze
mesh_terms: D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging; D005260:Female; D007958:Leukocyte Count; D009942:Organometallic Compounds / Q000008:administration & dosage*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010976:Platelet Count; D011817:Rabbits; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D012493:Samarium / Q000008:administration & dosage*
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011837:Radiation-Protective Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012493:Samarium; C061972:samarium Sm-153 lexidronam; D004999:Amifostine