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Hypocalcaemia after treatment with [177Lu-DOTA0,Tyr3]octreotate

European Journal of Nuclear Medicine and Molecular Imaging volume 40, pages 1843–1852 (2013)Cite this article

Abstract

Purpose

The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate).

Methods

In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group.

Results

In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17 %) showed a marked decrease in serum calcium levels with a nadir of ≤2.10 mmol/l. In five patients (11 %), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22 %) showed a serum calcium nadir of ≤2.10 mmol/l, and 11 (7 %) received calcium substitution therapy.

Conclusion

The mean serum calcium level decreased significantly after treatment with 177Lu-octreotate, resulting in mild hypocalcaemia in about 20 % of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.

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References

  1. Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001;12(7):941–5.

    PubMed  Article  CAS  Google Scholar 

  2. 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(5):610–6.

    PubMed  CAS  Google Scholar 

  3. 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(2):207–16.

    PubMed  Article  CAS  Google Scholar 

  4. Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med. 2006;36(2):147–56.

    PubMed  Article  Google Scholar 

  5. 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(13):2124–30.

    PubMed  Article  CAS  Google Scholar 

  6. Teunissen JJ, Krenning EP, de Jong FH, de Rijke YB, Feelders RA, van Aken MO, et al. Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function. Eur J Nucl Med Mol Imaging. 2009;36(11):1758–66.

    PubMed  Article  CAS  Google Scholar 

  7. 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  CAS  Google Scholar 

  8. 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(10):1847–56.

    PubMed  Article  CAS  Google Scholar 

  9. 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(17):2416–23.

    PubMed  Article  CAS  Google Scholar 

  10. Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med. 2001;28(9):1319–25.

    PubMed  Article  CAS  Google Scholar 

  11. Druckenthaner M, Schwarzer C, Ensinger C, Gabriel M, Prommegger R, Riccabona G, et al. Evidence for Somatostatin receptor 2 in thyroid tissue. Regul Pept. 2007;138(1):32–9.

    PubMed  Article  CAS  Google Scholar 

  12. Kwekkeboom DJ, Kam BL, van Essen M, Teunissen JJ, van Eijck CH, Valkema R, et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer. 2010;17(1):R53–73.

    PubMed  Article  CAS  Google Scholar 

  13. Glazebrook GA. Effect of decicurie doses of radioactive iodine 131 on parathyroid function. Am J Surg. 1987;154(4):368–73.

    PubMed  Article  CAS  Google Scholar 

  14. Guven A, Salman S, Boztepe H, Yarman S, Tanakol R, Azizlerli H, et al. Parathyroid changes after high dose radioactive iodine in patients with thyroid cancer. Ann Nucl Med. 2009;23(5):437–41.

    PubMed  Article  CAS  Google Scholar 

  15. Michaud LB, Goodin S. Cancer-treatment-induced bone loss, part 1. Am J Health Syst Pharm. 2006;63(5):419–30.

    PubMed  Article  Google Scholar 

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Acknowledgments

We thank all the personnel of the Department of Nuclear Medicine, the Department of Internal Medicine, and the Endocrinology Laboratory of Erasmus University Medical Centre for their expert help and cooperation. Special thanks are due to our research nurses Daniëlle Verwaal, Els Montijn, Agnes Keursten and Carla van ‘t Noordende, and to the medical nuclear analytical assistants Agnes de Lange, Carlijn Roozemond and Shahriar Tahmasebi.

Conflicts of interest

We disclose the following conflicts of interest:

  • Eric P. Krenning: Research support: Covidien, Novartis; Consultant: BioSynthema (AAA); Stockholder: Advanced Accelerator Applications (AAA)

  • Dik J. Kwekkeboom: Stockholder: Advanced Accelerator Applications (AAA)

The other authors declare that they have no conflicts of interest.

Author information

Affiliations

  1. Department of Nuclear Medicine, Erasmus MC, University Medical Center, ‘s Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands

    Esther I. van Vliet, Boen L. R. Kam, Jaap J. M. Teunissen, Eric P. Krenning & Dik J. Kwekkeboom

  2. Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    Wouter W. de Herder, M. Carola Zillikens & Robin P. Peeters

  3. Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    Yolanda B. de Rijke

Authors
  1. Esther I. van Vliet
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  2. Wouter W. de Herder
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  3. Yolanda B. de Rijke
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  4. M. Carola Zillikens
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  5. Boen L. R. Kam
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  6. Jaap J. M. Teunissen
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  7. Robin P. Peeters
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  8. Eric P. Krenning
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  9. Dik J. Kwekkeboom
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Correspondence to Esther I. van Vliet.

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van Vliet, E.I., de Herder, W.W., de Rijke, Y.B. et al. Hypocalcaemia after treatment with [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med Mol Imaging 40, 1843–1852 (2013). https://doi.org/10.1007/s00259-013-2503-y

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  • DOI: https://doi.org/10.1007/s00259-013-2503-y

Keywords

  • Neuroendocrine tumour
  • [177Lu-DOTA0,Tyr3]octreotate
  • Side effects
  • Hypocalcaemia