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A comparison of 111In-DOTATOC and 111In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours

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Abstract

[Yttrium-90-DOTA-Tyr3]-octreotide (DOTATOC) and [177Lu-DOTA-Tyr3-Thr8]-octreotide (DOTATATE) are used for peptide receptor-mediated radionuclide therapy (PRMRT) in neuroendocrine tumours. No human data comparing these two compounds are available so far. We used 111In as a surrogate for 90Y and 177Lu and examined whether one of the 111In-labelled peptides had a more favourable biodistribution in patients with neuroendocrine tumours. Special emphasis was given to kidney uptake and tumour-to-kidney ratio since kidney toxicity is usually the dose-limiting factor. Five patients with metastatic neuroendocrine tumours were injected with 222 MBq 111In-DOTATOC and 111In-DOTATATE within 2 weeks. Up to 48 h after injection, whole-body scans were performed and blood and urine samples were collected. The mean absorbed dose was calculated for tumours, kidney, liver, spleen and bone marrow. In all cases 111In-DOTATATE showed a higher uptake (%IA) in kidney and liver. The amount of 111In-DOTATOC excreted into the urine was significantly higher than for 111In-DOTATATE. The mean absorbed dose to the red marrow was nearly identical. 111In-DOTATOC showed a higher tumour-to-kidney absorbed dose ratio in seven of nine evaluated tumours. The variability of the tumour-to-kidney ratio was high and the significance level in favour of 111In-DOTATOC was P=0.065. In five patients the pharmacokinetics of 111In-DOTATOC and 111In-DOTATATE was found to be comparable. The two peptides appear to be nearly equivalent for PRMRT in neuroendocrine tumours, with minor advantages for 111In/90Y-DOTATOC; on this basis, we shall continue to use 90Y-DOTATOC for PRMRT in patients with metastatic neuroendocrine tumours.

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References

  1. Reubi JC, Laissue JA. Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol Sci 1995;16:110–5

    Article  CAS  PubMed  Google Scholar 

  2. Krenning EP, Kwekkeboom DJ, Bakker WH et al. Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–31

    CAS  PubMed  Google Scholar 

  3. Waldherr C, Pless M, Maecke H, Schumacher T, Crazzolara A, Nitzsche E, Haldemann A, Mueller-Brand J. Tumor response and clincical benefit in neuroendocrine tumors after 7.4 GBq 90Y-DOTATOC. J Nucl Med 2002;43:610–6

    Google Scholar 

  4. Kwekkeboom D, Bakker W, Kam BLR, Teunissen J, Kooij P, Herder W, Feelders R, Eijck C, Jong M, Srinivasan A, Erion J, Krenning E. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0, Tyr3]octreotate. Eur J Nucl Med 2003;30:417–22

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. Paganelli G, Bodei L, Handkiewicz Junak D, Rocca P, Papi S, Lopera Sierra M, Gatti M, Chinol M, Bartolomei M, Fiorenza M, Grana C. 90Y-DOTA-d-Phe1-Tyr3-octreotide in therapy of neuroendocrine malignancies. Biopolymers 2002;66:393–8

    Article  CAS  PubMed  Google Scholar 

  7. Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, Schmidt MA, Bugaj JL, de Jong M, Krenning EP. [177Lu-DOTA0Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001;28:1319–25

    CAS  PubMed  Google Scholar 

  8. Reubi J, Schaer J, Waser B, Wenger S, Heppeler A, Schmitt J, Maecke H. Affinity profiles for human somatostatin receptor subtypes SST1–SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000;27:273–82

    CAS  PubMed  Google Scholar 

  9. Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, Caracciolo M, Maecke H, Chinol M, Paganelli G. 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

    CAS  Google Scholar 

  10. Cremonesi M, Ferrari M, Zoboli S, Chinol M, Stabin M, Orsi F, Maecke H, Jermann E, Robertson C, Fiorenza M, Tosi G, Paganelli G. Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC. Eur J Nucl Med 1999;26:877–86

    CAS  PubMed  Google Scholar 

  11. Förster GJ, Engelbach M, Brockmann J, Reber H, Buchholz H-G, Maecke HR, Rösch F, Herzog H, Bartenstein P. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of 86Y-DOTATOC and 111In-DTPA-octreotide. Eur J Nucl Med 2001;28:1743–50

    CAS  PubMed  Google Scholar 

  12. Krenning EP, de Jong M, Jamar F, Valkema R, Kwekkeboom DJ, Kvols LK, Smith C, Pauwels E. Somatostatin receptor-targeted radiotherapy of tumors: preclinical and clinical findings. In: Lamberts S, Dogliotti L, eds. The expanding role of octreotide I: advances in oncology. Bristol: BioScientifica; 2002:211–23

  13. Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, De Camps J, Schran H, Chen T, Smith MC, Bouterfa H, Valkema R, Krenning EP, Kvols LK, Pauwels S. 86Y-DOTA0-d-Phe1-Tyr3-octreotide (SMT 487)—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

    CAS  PubMed  Google Scholar 

  14. Wild D, Schmitt JS, Ginj M, Maecke HR, Bernard BF, Krenning E, De Jong M, Wenger S, Reubi JC. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging 2003;30:1338–47

    Article  CAS  PubMed  Google Scholar 

  15. Heppeler A, Froidevaux S, Mäcke HR, Jermann E, Béhé M, Powell P, Hennig M. Radiometal-labelled macrocyclic chelator-derivatised somatostatin analogue with superb tumour-targeting properties and potential for receptor-mediated internal radiotherapy. Chem Eur J 1999;5:1016–23

    Article  Google Scholar 

  16. Erion J, Schmidt M, Wilhelm R, Achilefu S, Srinivasan A. Biodistribution and radiotherapy studies using samarium-153 and lutetium-177 DTPA conjugates of Y3-Octreotate. J Nucl Med 1999;40(Suppl):223

    Google Scholar 

  17. de Jong M, Bakker WH, Krenning EP, Breeman WA, van der Pluijm ME, Bernard BF, Visser TJ, Jermann E, Béhé M, Powell P, Maecke HR. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med 1997;24:368–71

    Article  PubMed  Google Scholar 

  18. Froidevaux S, Eberle AN, Christe M, Sumanovski L, Heppeler A, Schmitt JS, Eisenwiener K, Beglinger C, Maecke HR. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model. Int J Cancer 2002;98:930–7

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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;25:201–12

    CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank all supporting personnel of the Division of Radiological Chemistry, especially P. Powell, and the Institute of Nuclear Medicine, especially I. Gutierrez, for their expert help and effort. This work was supported by the Swiss National Foundation (project 3100 AO-100390) and was performed within the COST B12 action. We also wish to thank Drs. M. Konijnenberg (Tyco Healthcare, Petten, The Netherlands) and H. Roser and Prof. J. Roth (Division of Medical Physics, University Hospital Basel) for valuable discussions.

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Forrer, F., Uusijärvi, H., Waldherr, C. et al. A comparison of 111In-DOTATOC and 111In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 31, 1257–1262 (2004). https://doi.org/10.1007/s00259-004-1553-6

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  • DOI: https://doi.org/10.1007/s00259-004-1553-6

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