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- W191881421 abstract "1159 Objectives Radiolabeled peptides used for peptide-receptor radiotherapy are excreted via the kidneys and are partly reabsorbed in the proximal tubular cells, limiting the maximum activity dose that can be administered. The scavenger receptor megalin has been shown to play a role in the reabsorption of In-111-octreotide. In this study we aim to define the role of megalin in the reabsorption of various radiolabeled peptides using small animal SPECT and biodistribution studies of megalin-deficient mice. Methods Wild type (WT) and kidney-specific megalin-deficient mice (megalinlox/lox, ApoECre, female and male, n=4-6 per group) were injected with In-111-DTPA-labeled octreotide, octreotate, exendin, neurotensin or minigastrin analogs. Renal uptake was determined by SPECT scans at 3h and 24h post-injection (p.i.) or by dissection at 3h p.i. Kidney sections were immunostained for megalin. Results Renal retention of all studied peptides was 38-77% lower in megalin-deficient mice than in WT mice (tab.1). Autoradiography and SPECT data showed reduced uptake in the renal cortex of megalin-deficient mice. Immunohistochemistry confirmed reduced expression of megalin in the renal cortex of megalin-deficient mice. The correlation between SPECT and biodistribution data was excellent (r2=0,85). Conclusions Renal accumulation of all radiolabeled peptides was significantly lower in megalin-deficient mice, indicating that megalin plays an important role in the renal uptake of these peptides. Small animal SPECT is an accurate and useful tool to study renal uptake in vivo, enabling serial measurements in the same animal" @default.
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- W191881421 date "2010-05-01" @default.
- W191881421 modified "2023-09-27" @default.
- W191881421 title "Megalin is essential for the kidney uptake of In-111-labeled peptides: Studies in megalin-deficient mice" @default.
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