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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2007

01-12-2007 | Original article

Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics

Authors: A. R. Stahl, B. Wagner, T. Poethko, M. Perutka, H. J. Wester, M. Essler, U. Heemann, M. Schwaiger, J. Lutz

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2007

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Abstract

Aim

Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethason) as well as diuresis (furosemide and mannitol) regarding renal uptake of [111In]DOTATOC.

Methods

One hundred eight male Fisher rats were injected with [111In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats.

Results

Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake.

Conclusion

Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies.
Literature
1.
Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 2002;43:610–616.PubMed
2.
Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med 2001;28:1552–1554.PubMedCrossRef
3.
Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med 2005;46(Suppl 1):83S–91S.PubMed
4.
de Jong M, Barone R, Krenning E, Bernard B, Melis M, Visser T, et al. Megalin is essential for renal proximal tubule reabsorption of (111)In-DTPA-octreotide. J Nucl Med 2005;46:1696–1700.PubMed
5.
6.
Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. (86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487)—a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003;30:510–518.PubMedCrossRef
7.
van Eerd JE, Vegt E, Wetzels JF, Russel FG, Masereeuw R, Corstens FH, et al. Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J Nucl Med 2006;47:528–533.PubMed
8.
Vegt E, Wetzels JF, Russel FG, Masereeuw R, Boerman OC, van Eerd JE, et al. Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin. J Nucl Med 2006;47:432–436.PubMed
9.
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;37:1388–1392.PubMed
10.
Tahara H, Kusuhara H, Endou H, Koepsell H, Imaoka T, Fuse E, et al. A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther 2005;315:337–345.PubMedCrossRef
11.
Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, et al. Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther 2002;301:797–802.PubMedCrossRef
12.
Schottelius M, Schwaiger M, Wester HJ. Rapid and high-yield solution phase synthesis of DOTA-Tyr3-octreotide and DOTA-Tyr3-octreotate using unprotected DOTA. Tetrahedron Lett 2003;44:2393–2396.CrossRef
13.
Rolleman EJ, Valkema R, de Jong M, Kooij PP, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging 2003;30:9–15.PubMedCrossRef
14.
Shikano N, Kawai K, Flores LG 2nd, Nishii R, Kubota N, Ishikawa N, et al. An artificial amino acid, 4-iodo-L-meta-tyrosine: biodistribution and excretion via kidney. J Nucl Med 2003;44:625–631.PubMed
15.
Benet LZ. Pharmacokinetics/pharmacodynamics of furosemide in man: a review. J Pharmocokin Biopharm 1979;7:1–27.CrossRef
Metadata
Title
Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics
Authors
A. R. Stahl
B. Wagner
T. Poethko
M. Perutka
H. J. Wester
M. Essler
U. Heemann
M. Schwaiger
J. Lutz
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0519-x

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