W. Brenner et al., High-dose treatment with Re-186-HEDP or Sm-153-EDTMP combined with amifostine in a rabbit model, J NUCL MED, 42(10), 2001, pp. 1545-1550
Citations number
33
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Medical Research Diagnosis & Treatment
The aim of this experimental study was to investigate the myeloprotective p
otential of amifostine in rabbits receiving high-dose treatment with either
Sm-153-ethylenediaminetetramethylene phosphonate (EDTMP) or Re-186-hydroxy
ethylidene diphosphonate (HEDP) and to check for drug interactions impairin
g the skeletal uptake of these radiopharmaceuticals by amifostine. Methods:
To a total of 24 rabbits, we administered 1,000 MBq of either Sm-153-EDTMP
(n = 12) or Re-186-HEDP (n = 12). Six animals of each group received 500 m
g amifostine intravenously 10-15 min before injection of the radiopharmaceu
tical, whereas the other 6 animals served as controls. Up to 8 wk after tre
atment, blood samples were collected every 3-5 d to measure platelet and le
ukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h,
and 24 h after injection of the radiopharmaceutical to quantify the skelet
al uptake. Results: For 186Re-HEDP, the mean decrease in platelets was sign
ificantly 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-ED
TMP (36.5% +/- 8.3% vs. 52.3% +/- 14.0%, P < 0.05). No significant differen
ces in leukocyte counts were found for 186Re-HEDP (75.3% +/- 12.3% in the a
mifostine group and 72.5% +/- 4.1% in the control group, P > 0.05), whereas
rabbits treated with Sm-153-EDTMP plus amifostine showed a significantly g
reater 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-bo
dy 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 Sm-153-EDTMP (31.7% +/- 8.9% vs. 44.0% +/- 6.5
%, P < 0.05). Conclusion: For amifostine, we found a highly significant cyt
oprotective effect on platelets but no leukoprotective effect. The latter p
robably relies on the intrinsic myelotoxicity of high-dose amifostine, whic
h seemed to potentiate the leukodepression of the radiopharmaceuticals. The
lower bone uptake in amifostine-treated animals may be caused by the chemi
cal structure of amifostine, which is a potentially complex-forming compoun
d that may be able to displace bisphosphonates from the rhenium- and samari
um-bisphosphonate complexes, resulting in altered biodistribution patterns.