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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Vegt, E. Articles by Boerman, O. PubMed Articles by Vegt, E. Articles by Boerman, O.

Inhibition of renal uptake of radiolabeled peptides using fragments of albumin

¹ Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; ² Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands

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Objectives: In peptide receptor radionuclide therapy the kidney is the dose-limiting organ. Several agents have been identified that can reduce renal uptake of peptides by interfering with megalin-mediated reabsorption. Since albumin is a well-known megalin ligand, we hypothesized that albumin(ALB) might be a potent inhibitor of renal reabsorption of radiolabeled peptides. Because only a small fraction of intact albumin passes the glomerulus, we studied the use of fragments of albumin (FRALB) to reduce the renal uptake of In-111-labeled peptides.

Methods: In order to study the reduction of renal uptake of In-111-octreotide, rats were injected with 0.5 mL PBS, lysine, Gelofusine, ALB or FRALB, followed immediately by i.v. injection of In-111-octreotide. Kidney uptake of In-111-octreotide was measured 20 h p.i. Reduction of renal uptake of In-111-labeled exendin-4 and minigastrin by FRALB was determined.

Results: Renal uptake of In-111-labeled FRALB was significantly higher than that of ALB (P<0.001). Co-administration of FRALB reduced renal uptake of In-111-octreotide with 45% (0.65 %ID/g vs. 1.18 %ID/g). Administration of 1-2 mg FRALB, with a molecular weight between 3 and 50 kD, reduced renal In-111-octreotide uptake as effectively as 80 mg lysine. Moreover, FRALB reduced renal uptake of In-111-labeled exendin-4 and minigastrin by 50% and 92%, respectively.

Conclusions: Renal uptake of In-111-labeled octreotide, exendin-4 and minigastrin can be effectively reduced in rats by administration of albumin fragments. Fragments with a molecular weight between 3 and 50 kD reduced renal uptake of In-111-octreotide most efficiently. We aim to identify the exact albumin fragments that are responsible for blockade of renal In-111-octreotide uptake.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Vegt, E. Articles by Boerman, O. PubMed Articles by Vegt, E. Articles by Boerman, O.