Albumin derived peptides efficiently reduce renal uptake of radiolabeled peptides

Objectives In peptide receptor radionuclide therapy the kidney is the dose-limiting organ. Several agents can reduce renal retention of radiolabeled peptides by interfering with receptor-mediated endocytosis. We found that trypsinized bovine serum albumin (BSA) is a potent inhibitor of renal reabsorption of In-111-labeled peptides.Objective: To identify clinically useful inhibitors of renal uptake of radiolabeled peptides by synthesizing chemically defined BSA derived peptides, thereby gaining more insight in the mechanisms of renal reabsorption.

Methods Six sections of the BSA molecule with varying numbers of positive and negative charges were synthesized (16 to 36 amino acids in length). The potency of these peptides to reduce binding of In-111-labeled octreotide, exendin and minigastrin to megalin-expressing cells was studied in vitro. The most potent peptide was selected for in vivo testing in rats. This peptide and a negative and a positive control were injected i.v., followed by In-111-labeled octreotide, exendin or minigastrin. Renal uptake was measured 20 h p.i.

Results The inhibitory potency of the BSA-derived peptides varied widely. In vitro, the most potent peptide reduced binding of exendin by 94% and minigastrin by 96%. In rats, the renal retention of octreotide, exendin and minigastrin was reduced by 33%, 26% and 88%, respectively. The effect of 5 mg of the BSA-derived peptide was comparable to the effect of 20 mg Gelofusine.

Conclusions Renal uptake of In-111-labeled octreotide, exendin and minigastrin can be effectively reduced in rats by administration of a BSA-derived peptide.