Purpose: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Methods: Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of111In-albumin,111In-minigastrin,111In-exendin and111In- octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of111In-minigastrin,111In-exendin and111In-octreotide was determined. Results: FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of111In-albumin,111In-exendin and111In- minigastrin in vitro. The most efficient albumin-derived peptide (peptide #6), was selected for in vivo testing. In rats, 5 mg of peptide #6 very efficiently inhibited the renal uptake of111In-minigastrin, by 88%. Uptake of111In-exendin and111In-octreotide was reduced by 26 and 33%, respectively. Conclusions: The albumin-derived peptide #6 efficiently inhibited the renal reabsorption of111In-minigastrin,111In-exendin and111In-octreotide and is a promising candidate for kidney protection in PRRT.

Additional Metadata
Keywords Albumin, Exendin, Kidney, Minigastrin, Octreotide, Peptide-receptor radionuclide therapy
Persistent URL dx.doi.org/10.1007/s00259-009-1239-1, hdl.handle.net/1765/28625
Journal European Journal of Nuclear Medicine and Molecular Imaging
Vegt, E, Eek, A, Oyen, W.J, de Jong, M, Gotthardt, M, & Boerman, O.C. (2010). Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides. European Journal of Nuclear Medicine and Molecular Imaging, 37(2), 226–234. doi:10.1007/s00259-009-1239-1