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Open Access 01-12-2016 | Original research

Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of ¹⁶¹Tb-folate and ¹⁷⁷Lu-folate

Authors: Stephanie Haller, Giovanni Pellegrini, Christiaan Vermeulen, Nicholas P. van der Meulen, Ulli Köster, Peter Bernhardt, Roger Schibli, Cristina Müller

Published in: EJNMMI Research | Issue 1/2016

Abstract

Background

The radiolanthanide ¹⁶¹Tb has, in recent years, attracted increasing interest due to its favorable characteristics for medical application. ¹⁶¹Tb exhibits similar properties to the widely-used therapeutic radionuclide ¹⁷⁷Lu. In contrast to ¹⁷⁷Lu, ¹⁶¹Tb yields a significant number of short-ranging Auger/conversion electrons (≤50 keV) during its decay process. ¹⁶¹Tb has been shown to be more effective for tumor therapy than ¹⁷⁷Lu if applied using the same activity. The purpose of this study was to investigate long-term damage to the kidneys after application of ¹⁶¹Tb-folate and compare it to the renal effects caused by ¹⁷⁷Lu-folate.

Methods

Renal side effects were investigated in nude mice after the application of different activities of ¹⁶¹Tb-folate (10, 20, and 30 MBq per mouse) over a period of 8 months. Renal function was monitored by the determination of ^99mTc-DMSA uptake in the kidneys and by measuring blood urea nitrogen and creatinine levels in the plasma. Histopathological analysis was performed by scoring of the tissue damage observed in HE-stained kidney sections from euthanized mice.

Results

Due to the co-emitted Auger/conversion electrons, the mean absorbed renal dose of ¹⁶¹Tb-folate (3.0 Gy/MBq) was about 24 % higher than that of ¹⁷⁷Lu-folate (2.3 Gy/MBq). After application of ¹⁶¹Tb-folate, kidney function was reduced in a dose- and time-dependent manner, as indicated by the decreased renal uptake of ^99mTc-DMSA and the increased levels of blood urea nitrogen and creatinine. Similar results were obtained when ¹⁷⁷Lu-folate was applied at the same activity. Histopathological investigations confirmed comparable renal cortical damage after application of the same activities of ¹⁶¹Tb-folate and ¹⁷⁷Lu-folate. This was characterized by collapsed tubules and enlarged glomeruli with fibrin deposition in moderately injured kidneys and glomerulosclerosis in severely damaged kidneys.

Conclusions

Tb-folate induced dose-dependent radionephropathy over time, but did not result in more severe damage than ¹⁷⁷Lu-folate when applied at the same activity. These data are an indication that Auger/conversion electrons do not exacerbate overall renal damage after application with ¹⁶¹Tb-folate as compared to ¹⁷⁷Lu-folate, even though they result in an increased dose deposition in the renal tissue. Global toxicity affecting other tissues than kidneys remains to be investigated after ¹⁶¹Tb-based therapy, however.

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Title: Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of 161Tb-folate and 177Lu-folate
Authors: Stephanie Haller
Giovanni Pellegrini
Christiaan Vermeulen
Nicholas P. van der Meulen
Ulli Köster
Peter Bernhardt
Roger Schibli
Cristina Müller
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-016-0171-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of ¹⁶¹Tb-folate and ¹⁷⁷Lu-folate

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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