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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2007

01-05-2007 | Original Article

Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

Authors: Edgar J. Rolleman, Flavio Forrer, Bert Bernard, Magda Bijster, Marcel Vermeij, Roelf Valkema, Eric P. Krenning, Marion de Jong

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2007

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Abstract

Purpose

In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [177Lu-DOTA0,Tyr3]octreotate.

Methods

Male Lewis rats were injected with 278 or 555 MBq [177Lu-DOTA0,Tyr3]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99mTc-dimercaptosuccinic acid (DMSA), a measure of tubular function.

Results

Treatment with 555 MBq [177Lu-DOTA0,Tyr3]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [177Lu-DOTA0,Tyr3]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of 99mTc-DMSA SPECT scintigrams at 130 days after [177Lu-DOTA0,Tyr3]octreotate therapy correlated well with 1/creatinine (r 2=0.772, p<0.001).

Conclusion

Amifostine and lysine effectively decreased functional renal damage caused by high-dose [177Lu-DOTA0,Tyr3]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy.
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Metadata
Title
Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate
Authors
Edgar J. Rolleman
Flavio Forrer
Bert Bernard
Magda Bijster
Marcel Vermeij
Roelf Valkema
Eric P. Krenning
Marion de Jong
Publication date
01-05-2007
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0291-3

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