Reducing renal uptake of radiolabeled peptides using albumin fragments

In most types of peptide receptor radionuclide therapy, the max-imum activity dose that can be administered is limited by high and persistent renal retention of the radiolabeled peptides, which is, at least partly, mediated by the megalin receptor. Several agents that interfere with renal reabsorption of radiolabeled pep-tides have been identified (e.g., lysine, arginine, succinylated gel-atin solution), but none of these inhibit renal reabsorption completely. Albumin, a naturally abundant megalin ligand, might be a safe and potent alternative. In this study, we analyzed the effects of albumin and fragments of albumin (FRALB) on the renal reabsorption of 111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide (111In-octreotide), [Lys40(aminohexoic acid-DTPA-111In)NH2]-exendin-4 (111In-exendin), and 111In-1,4,7,10-tetraazacyclododecane-N,N9,N$,N9$-tetraacetic acid (DOTA)-Glu1-minigastrin (111In-minigastrin). Methods: The ef-fects of albumin and FRALB on megalin-associated binding o