nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.10.2005 | Original Article

Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

verfasst von: Marleen Melis, Eric P. Krenning, Bert F. Bernard, Raffaella Barone, Theo J. Visser, Marion de Jong

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 10/2005

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues.

Methods

For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1–24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [¹¹¹In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats.

Results

Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [¹¹¹In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [¹¹¹In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control.

Conclusion

Renal retention of [¹¹¹In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part.

Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [¹¹¹In-DTPA-d-Phe¹]- and [¹²³I-Tyr³]-octreotide: the Rotterdam experience with more than 1,000 patients. Eur J Nucl Med 1993;20:716–31PubMed

Kwekkeboom DJ, Krenning EP. Somatostatin receptor imaging. Semin Nucl Med 2002;32:84–91CrossRefPubMed

de Jong M, Kwekkeboom D, Valkema R, Krenning EP. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002. Eur J Nucl Med Mol Imaging 2003;30:463–9PubMed

Krenning EP, Kwekkeboom DJ, Valkema R, Pauwels S, Kvols LK, De Jong M. Peptide receptor radionuclide therapy. Ann N Y Acad Sci 2004;1014:234–45CrossRefPubMed

Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26:1439–47CrossRefPubMed

Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, et al. Receptor-mediated radiotherapy with⁹⁰Y-DOTA-d-Phe¹-Tyr³-octreotide. Eur J Nucl Med 2001;28:426–34

Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22PubMed

De Jong M, Valkema R, Van Gameren A, Van Boven H, Bex A, Van De Weyer EP, et al. Inhomogeneous localization of radioactivity in the human kidney after injection of [¹¹¹In-DTPA]octreotide. J Nucl Med 2004;45:1168–71PubMed

Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet 2004;19:159–70CrossRefPubMed

10.

Christensen EI, Birn H. Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol 2001;280:F562–73PubMed

11.

Verroust PJ, Christensen EI. Megalin and cubilin—the story of two multipurpose receptors unfolds. Nephrol Dial Transplant 2002;17:1867–71CrossRefPubMed

12.

Christensen EI, Nielsen S, Moestrup SK, Borre C, Maunsbach AB, de Heer E, et al. Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules. Eur J Cell Biol 1995;66:349–64PubMed

13.

Bakker WH, Krenning EP, Reubi JC, Breeman WA, Setyono-Han B, de Jong M, et al. In vivo application of [¹¹¹In-DTPA-d-Phe¹]-octreotide for detection of somatostatin receptor-positive tumors in rats. Life Sci 1991;49:1593–601CrossRefPubMed

14.

de Jong M, Breeman WA, Bernard BF, Bakker WH, Schaar M, van Gameren A, et al. [¹⁷⁷Lu-DOTA(0),Tyr³] octreotate for somatostatin receptor-targeted radionuclide therapy. Int J Cancer 2001;92:628–33CrossRefPubMed

15.

Breeman WA, De Jong M, Visser TJ, Erion JL, Krenning EP. Optimising conditions for radiolabelling of DOTA-peptides with⁹⁰Y, ¹¹¹In and ¹⁷⁷Lu at high specific activities. Eur J Nucl Med Mol Imaging 2003;30:917–20PubMed

16.

de Jong M, Breeman WA, Bakker WH, Kooij PP, Bernard BF, Hofland LJ, et al. Comparison of¹¹¹In-labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy. Cancer Res 1998;58:437–41PubMed

17.

Akizawa H, Arano Y, Mifune M, Iwado A, Saito Y, Uehara T, et al. Significance of¹¹¹In-DTPA chelate in renal radioactivity levels of¹¹¹In-DTPA-conjugated peptides. Nucl Med Biol 2001;28:459–68CrossRefPubMed

18.

Ten Bokum AM, Rosmalen JG, Hofland LJ, Krenning EP, Van Hagen PM, Breeman WA. Tissue distribution of octreotide binding receptors in normal mice and strains prone to autoimmunity. Nucl Med Commun 2002;23:1009–17CrossRefPubMed

19.

Mogensen CE, Solling. Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest 1977;37:477–86

20.

Behr TM, Goldenberg DM, 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;25:201–12CrossRefPubMed

21.

Hofland LJ, Lamberts SW, van Hagen PM, Reubi JC, Schaeffer J, Waaijers M, et al. Crucial role for somatostatin receptor subtype 2 in determining the uptake of [¹¹¹In-DTPA-d-Phe¹]octreotide in somatostatin receptor-positive organs. J Nucl Med 2003;44:1315–21PubMed

22.

Christensen EI, Rennke HG, Carone FA. Renal tubular uptake of protein: effect of molecular charge. Am J Physiol 1983;244:F436–41PubMed

23.

Akizawa H, Arano Y, Mifune M, Iwado A, Saito Y, Mukai T, et al. Effect of molecular charges on renal uptake of ¹¹¹In-DTPA-conjugated peptides. Nucl Med Biol 2001;28:761–8CrossRefPubMed

24.

Bernard BF, Krenning EP, Breeman WA, Rolleman EJ, Bakker WH, Visser TJ, et al. d-Lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med 1997;38:1929–33PubMed

25.

Behr TM, Sharkey RM, Juweid ME, Blumenthal RD, Dunn RM, Griffiths GL, et al. Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives. Cancer Res 1995;55:3825–34PubMed

26.

Kramer JH, Gonick HC. Experimental Fanconi syndrome: I. Effect of maleic acid on renal cortical Na–K-ATPase activity and ATP levels. J Lab Clin Med 1970;76:799–808PubMed

27.

Nagai J, Tanaka H Nakanishi N, Murakami T, Takano M. Role of megalin in renal handling of aminoglycosides. Am J Physiol Renal Physiol 2001;281:F337–44PubMed

28.

de Jong M, Rolleman EJ, Bernard BF, Visser TJ, Bakker WH, Breeman WA, et al. Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo. J Nucl Med 1996;37:1388–92PubMed

29.

Rolleman EJ, Krenning EP, Van Gameren A, Bernard BF, De Jong M. Uptake of [¹¹¹In-DTPA⁰]octreotide in the rat kidney is inhibited by colchicine and not by fructose. J Nucl Med 2004;45:709–13PubMed

30.

Gutmann EJ, Niles JL, McCluskey RT, Brown D. Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules. Am J Physiol 1989;257:C397–407PubMed

31.

Safirstein R, Winston J, Goldstein M, Moel D, Dikman S, Guttenplan J. Cisplatin nephrotoxicity. Am J Kidney Dis 1986;8:356–67PubMed

32.

Takano M, Nakanishi N, Kitahara Y, Sasaki Y, Murakami T, Nagai J. Cisplatin-induced inhibition of receptor-mediated endocytosis of protein in the kidney. Kidney Int 2002;62:1707–17CrossRefPubMed

33.

Choie DD, Longnecker DS, del Campo AA. Acute and chronic cisplatin nephropathy in rats. Lab Invest 1981;44:397–402PubMed

Titel: Localisation and mechanism of renal retention of radiolabelled somatostatin analogues
verfasst von: Marleen Melis
Eric P. Krenning
Bert F. Bernard
Raffaella Barone
Theo J. Visser
Marion de Jong
Publikationsdatum: 01.10.2005
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 10/2005
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-005-1793-0

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2005

A newly developed intra-operative gamma camera: performance characteristics in a laboratory phantom study

Global cognitive impairment should be taken into account in SPECT–neuropsychology correlations: the example of verbal memory in very mild Alzheimer’s disease

Development of a practical image-based scatter correction method for brain perfusion SPECT: comparison with the TEW method

PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients

Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

A publicly accessible Monte Carlo database for validation purposes in emission tomography