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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.12.2013 | Original Article

Rapid blood clearance and lack of long-term renal toxicity of ¹⁷⁷Lu-DOTATATE enables shortening of renoprotective amino acid infusion

verfasst von: Raghava Kashyap, Price Jackson, Michael S. Hofman, Peter Eu, Jean-Mathieu Beauregard, Diana Zannino, Rodney J. Hicks

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2013

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Abstract

Purpose

The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion.

Methods

The whole-blood clearance of ¹⁷⁷Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion.

Results

LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI −6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion.

Conclusion

The greatest renal exposure to circulating radiopeptide occurs in the first 1 – 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.

Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011;38:2125–35. doi:10.1007/s00259-011-1902-1.CrossRefPubMed

Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23. doi:10.1200/JCO.2010.33.7873.CrossRefPubMed

Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003;30:417–22. doi:10.1007/s00259-002-1050-8.CrossRefPubMed

Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30. doi:10.1200/JCO.2007.15.2553.CrossRefPubMed

Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005;23:2754–62. doi:10.1200/JCO.2005.08.066.CrossRefPubMed

Hubble D, Kong G, Michael M, Johnson V, Ramdave S, Hicks RJ. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging. 2010;37:1869–75. doi:10.1007/s00259-010-1483-4.CrossRefPubMed

Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:302–11. doi:10.1007/s00259-010-1631-x.CrossRefPubMed

Lambert B, Cybulla M, Weiner SM, Van De Wiele C, Ham H, Dierckx RA, et al. Renal toxicity after radionuclide therapy. Radiat Res. 2004;161:607–11.CrossRefPubMed

Vegt E, de Jong M, Wetzels JF, Masereeuw R, Melis M, Oyen WJ, et al. Renal toxicity of radiolabeled peptides and antibody fragments: mechanisms, impact on radionuclide therapy, and strategies for prevention. J Nucl Med. 2010;51:1049–58. doi:10.2967/jnumed.110.075101.CrossRefPubMed

10.

Melis M, Krenning EP, Bernard BF, Barone R, Visser TJ, de Jong M. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues. Eur J Nucl Med Mol Imaging. 2005;32:1136–43. doi:10.1007/s00259-005-1793-0.CrossRefPubMed

11.

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;26:1439–47.CrossRefPubMed

12.

van Essen M, Krenning EP, Kam BL, de Herder WW, van Aken MO, Kwekkeboom DJ. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35:743–8. doi:10.1007/s00259-007-0688-7.CrossRefPubMed

13.

Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med. 2001;28:1552–4. doi:10.1007/s002590100599.CrossRefPubMed

14.

Rolleman EJ, Melis M, Valkema R, Boerman OC, Krenning EP, de Jong M. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. Eur J Nucl Med Mol Imaging. 2010;37:1018–31. doi:10.1007/s00259-009-1282-y.CrossRefPubMed

15.

Hammond PJ, Wade AF, Gwilliam ME, Peters AM, Myers MJ, Gilbey SG, et al. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue. Br J Cancer. 1993;67:1437–9.CrossRefPubMed

16.

Kwekkeboom DJ, Krenning EP, Lebtahi R, Komminoth P, Kos-Kudla B, de Herder WW, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology. 2009;90:220–6. doi:10.1159/000225951.CrossRefPubMed

17.

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;30:510–8. doi:10.1007/s00259-003-1117-1.CrossRefPubMed

18.

Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging. 2003;30:207–16. doi:10.1007/s00259-002-1023-y.CrossRefPubMed

19.

Barone R, Pauwels S, De Camps J, Krenning EP, Kvols LK, Smith MC, et al. Metabolic effects of amino acid solutions infused for renal protection during therapy with radiolabelled somatostatin analogues. Nephrol Dial Transplant. 2004;19:2275–81. doi:10.1093/ndt/gfh362.CrossRefPubMed

20.

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. doi:10.1007/s00259-002-0982-3.CrossRefPubMed

21.

Beauregard JM, Hofman MS, Pereira JM, Eu P, Hicks RJ. Quantitative 177Lu SPECT (QSPECT) imaging using a commercially available SPECT/CT system. Cancer Imaging. 2011;11:56–66. doi:10.1102/1470-7330.2011.0012.CrossRefPubMed

22.

Giovacchini G, Nicolas G, Freidank H, Mindt TL, Forrer F. Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy. Eur J Nucl Med Mol Imaging. 2011;38:1675–82. doi:10.1007/s00259-011-1826-9.CrossRefPubMed

23.

Hartlev LB, Boeje CR, Bluhme H, Palshof T, Rehling M. Monitoring renal function during chemotherapy. Eur J Nucl Med Mol Imaging. 2012;39:1478–82. doi:10.1007/s00259-012-2158-0.CrossRefPubMed

24.

Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc. 1985;33:278–85.PubMed

25.

Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008;35:1847–56. doi:10.1007/s00259-008-0778-1.CrossRefPubMed

26.

Beauregard JM, Hofman MS, Kong G, Hicks RJ. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39:50–6. doi:10.1007/s00259-011-1937-3.CrossRefPubMed

Titel: Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion
verfasst von: Raghava Kashyap
Price Jackson
Michael S. Hofman
Peter Eu
Jean-Mathieu Beauregard
Diana Zannino
Rodney J. Hicks
Publikationsdatum: 01.12.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2013
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2504-x

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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