Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides.
OBJECTIVE
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 of (111)In-albumin, (111)In-minigastrin, (111)In-exendin and (111)In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of (111)In-minigastrin, (111)In-exendin and (111)In-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 of (111)In-albumin, (111)In-exendin and (111)In-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 of (111)In-minigastrin, by 88%. Uptake of (111)In-exendin and (111)In-octreotide was reduced by 26 and 33%, respectively.


CONCLUSIONS
The albumin-derived peptide #6 efficiently inhibited the renal reabsorption of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide and is a promising candidate for kidney protection in PRRT.
Vegt
Erik
E
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. erikvegt@gmail.com
Eek
Annemarie
A
Oyen
Wim J G
WJ
de Jong
Marion
M
Gotthardt
Martin
M
Boerman
Otto C
OC
D000418:Albumins / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D000418:Albumins; D007205:Indium Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals