Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model.
BACKGROUND
Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model.


METHODS
Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically.


RESULTS
Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals.


CONCLUSIONS
Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.
Bohuslavizki
K H
KH
Department of Nuclear Medicine, University Hospital Eppendorf, Hamburg, Germany. bohu@uke.uni-hamburg.de
Klutmann
S
S
Jenicke
L
L
Brenner
W
W
Feyerabend
B
B
Henze
E
E
Clausen
M
M
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007457:Iodine Radioisotopes / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011853:Radiobiology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012469:Salivary Glands / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D011837:Radiation-Protective Agents; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D004999:Amifostine