HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brenner, W. Articles by Henze, E. Search for Related Content PubMed PubMed Citation Articles by Brenner, W. Articles by Henze, E.

High-Dose Treatment with ¹⁸⁶Re-HEDP or ¹⁵³Sm-EDTMP Combined with Amifostine in a Rabbit Model

Clinic of Nuclear Medicine, Christian-Albrechts-Universität, Kiel, Germany

The aim of this experimental study was to investigate the myeloprotective potential of amifostine in rabbits receiving high-dose treatment with either ¹⁵³Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or ¹⁸⁶Re-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 ¹⁵³Sm-EDTMP (n = 12) or ¹⁸⁶Re-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 ¹⁸⁶Re-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 ¹⁵³Sm-EDTMP (36.5% ± 8.3% vs. 52.3% ± 14.0%, P < 0.05). No significant differences in leukocyte counts were found for ¹⁸⁶Re-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 ¹⁵³Sm-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 ¹⁸⁶Re-HEDP (15.8% ± 3.1% vs. 30.9% ± 1.9%, P < 0.001) and ¹⁵³Sm-EDTMP (31.7% ± 8.9% vs. 44.0% ± 6.5%, P < 0.05). Conclusion: 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.

Key Words: amifostine • myeloprotection • ¹⁸⁶Re-hydroxyethylidene diphosphonate • ¹⁵³Sm-ethylenediaminetetramethylene phosphonate • skeletal uptake