Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient miceReport as inadecuate

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice - Download this document for free, or read online. Document in PDF available to download.

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 38, Issue 4, pp 623–632

First Online: 18 December 2010Received: 05 August 2010Accepted: 15 November 2010


PurposeRadiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated.

MethodsGroups of kidney-specific megalin-deficient mice and wild-type mice were injected with In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic SPECT images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured.

ResultsMegalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% In-octreotide to 65% In-exendin of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation.

ConclusionMegalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice.

KeywordsKidney Megalin Peptide receptor radionuclide therapy Octreotide Octreotate Exendin Neurotensin Minigastrin Erik Vegt and Marleen Melis contributed equally to this work.

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Author: Erik Vegt - Marleen Melis - Annemarie Eek - Monique de Visser - Maarten Brom - Wim J. G. Oyen - Martin Gotthardt - Mario


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