Albumin-derived Peptides Efficiently Reduce Renal Uptake of Radiolabelled Peptides

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2009 Sep 2

PMID 19722105

Citations 21

Authors

Erik Vegt

Annemarie Eek

Wim J G Oyen

Marion de Jong

Martin Gotthardt

Otto C Boerman

Affiliations

Soon will be listed here.

Abstract

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 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.

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References

Bernard B, Krenning E, Breeman W, Rolleman E, Bakker W, Visser T . D-lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med. 1998; 38(12):1929-33. View

Behr T, Goldenberg D, Becker W . Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med. 1998; 25(2):201-12. DOI: 10.1007/s002590050216. View

Vegt E, van Eerd J, Eek A, Oyen W, Wetzels J, de Jong M . Reducing renal uptake of radiolabeled peptides using albumin fragments. J Nucl Med. 2008; 49(9):1506-11. DOI: 10.2967/jnumed.108.053249. View

Pimm M, Gribben S . Prevention of renal tubule re-absorption of radiometal (indium-111) labelled Fab fragment of a monoclonal antibody in mice by systemic administration of lysine. Eur J Nucl Med. 1994; 21(7):663-5. DOI: 10.1007/BF00285590. View

Hnatowich D, Childs R, Lanteigne D, Najafi A . The preparation of DTPA-coupled antibodies radiolabeled with metallic radionuclides: an improved method. J Immunol Methods. 1983; 65(1-2):147-57. DOI: 10.1016/0022-1759(83)90311-3. View

OCarroll A . Localization of messenger ribonucleic acids for somatostatin receptor subtypes (sstr1-5) in the rat adrenal gland. J Histochem Cytochem. 2002; 51(1):55-60. DOI: 10.1177/002215540305100107. View

Behe M, Kluge G, Becker W, Gotthardt M, Behr T . Use of polyglutamic acids to reduce uptake of radiometal-labeled minigastrin in the kidneys. J Nucl Med. 2005; 46(6):1012-5. View

Skopp R, Lane L . Fingerprinting of proteins cleaved in solution by cyanogen bromide. Appl Theor Electrophor. 1988; 1(1):61-4. View

ORLANDO R, Exner M, Czekay R, Yamazaki H, Saito A, Ullrich R . Identification of the second cluster of ligand-binding repeats in megalin as a site for receptor-ligand interactions. Proc Natl Acad Sci U S A. 1997; 94(6):2368-73. PMC: 20094. DOI: 10.1073/pnas.94.6.2368. View

10.

Baines R, Brunskill N . The molecular interactions between filtered proteins and proximal tubular cells in proteinuria. Nephron Exp Nephrol. 2008; 110(2):e67-71. DOI: 10.1159/000161982. View

11.

Christensen E, Verroust P . Megalin and cubilin, role in proximal tubule function and during development. Pediatr Nephrol. 2002; 17(12):993-9. DOI: 10.1007/s00467-002-0956-5. View

12.

Cybulla M, Weiner S, Otte A . End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med. 2001; 28(10):1552-4. DOI: 10.1007/s002590100599. View

13.

van Eerd J, Vegt E, Wetzels J, Russel F, Masereeuw R, Corstens F . Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J Nucl Med. 2006; 47(3):528-33. View

14.

Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P . Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med. 1999; 26(11):1439-47. View

15.

Thelle K, Christensen E, Vorum H, Orskov H, Birn H . Characterization of proteinuria and tubular protein uptake in a new model of oral L-lysine administration in rats. Kidney Int. 2006; 69(8):1333-40. DOI: 10.1038/sj.ki.5000272. View

16.

Gekle M . Renal tubule albumin transport. Annu Rev Physiol. 2005; 67:573-94. DOI: 10.1146/annurev.physiol.67.031103.154845. View

17.

Mogensen C, Solling . Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest. 1977; 37(6):477-86. DOI: 10.3109/00365517709101835. View

18.

Vegt E, Wetzels J, Russel F, Masereeuw R, Boerman O, van Eerd J . Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin. J Nucl Med. 2006; 47(3):432-6. View

19.

Krempels K, Hunyady B, OCarroll A, Mezey E . Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract. Gastroenterology. 1997; 112(6):1948-60. DOI: 10.1053/gast.1997.v112.pm9178687. View

20.

Birn H, Christensen E . Renal albumin absorption in physiology and pathology. Kidney Int. 2006; 69(3):440-9. DOI: 10.1038/sj.ki.5000141. View