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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.02.2007 | Original article

Long-term toxicity of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate in rats

verfasst von: Edgar J. Rolleman, Eric P. Krenning, Bert F. Bernard, Monique de Visser, Magda Bijster, Theo J. Visser, Marcel Vermeij, Jan Lindemans, Marion de Jong

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2007

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Abstract

Purpose and methods

Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models.

Results

Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2×278 MBq groups. Three doses of 185 MBq [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l, respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria.

Conclusion

Injection of high doses of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage.

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Titel: Long-term toxicity of [177Lu-DOTA0,Tyr3]octreotate in rats
verfasst von: Edgar J. Rolleman
Eric P. Krenning
Bert F. Bernard
Monique de Visser
Magda Bijster
Theo J. Visser
Marcel Vermeij
Jan Lindemans
Marion de Jong
Publikationsdatum: 01.02.2007
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0232-1

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Long-term toxicity of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate in rats

Abstract

Purpose and methods

Results

Conclusion

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose and methods

Results

Conclusion

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