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Selective hepatic arterial infusion of In-111-DTPA-Phe1-octreotide in neuroendocrine liver metastases

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Abstract

Purpose

The aim of this study is to evaluate the effectiveness of 111In-DTPA-Phe1-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst2 receptor-positive neuroendocrine tumours due to the effect of 111In Auger electron emission, minimising in parallel the toxicity of non-target tissue.

Methods

The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function.

Results

Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases.

Conclusion

In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of 111In-DTPA-Phe1-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of 111In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.

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References

  1. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol. 1999;20:157–98.

    Article  PubMed  CAS  Google Scholar 

  2. Janson ET, Westlin J-E, Öhrvall U, Öberg K, Lukinius A. Nuclear localization of 111In after intravenous injections of [111In-DTPA-d-Phe1]-octreotide in patients with neuroendocrine tumors. J Nucl Med. 2000;41:1514–8.

    PubMed  CAS  Google Scholar 

  3. 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 1000 patients. Eur J Nucl Med. 1993;20:716–31.

    Article  PubMed  CAS  Google Scholar 

  4. De Jong M, Bernard BF, De Bruin E, Van Gameren A, Bakker WH, Visser TJ, et al. Internalization of radiolabelled [DTPA°]octreotide and [DOTA°, Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun. 1998;19:283–8.

    Article  PubMed  Google Scholar 

  5. Anderson P, Forssel-Aronsson E, Johanson V, Wängberg B, Nilsson O, Fjälling M, et al. Internalization of indium-111 into human neuroendocrine tumor cell after incubation with indium-11-DTPA-d-Phe1-octreotide. J Nucl Med. 1996;37:2002–6.

    Google Scholar 

  6. Bass LA, Lanahan MV, Duncan JR, Erion JL, Srinivasan A, Schmidt MA, et al. Identification of the soluble in vivo metabolites of indium-111-diethylenetriaminepentaacetic acid-d-Phe1-octreotide. Bioconjug Chem. 1998;9:192–200.

    Article  PubMed  CAS  Google Scholar 

  7. Krenning EP, Kooij PPM, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D.Phe1]-octreotide; a case history. Ann NY Acad Sci 1994;733:496–506.

    Article  PubMed  CAS  Google Scholar 

  8. Kaltsas GA, Stefanidou Z, Papadogias D, Grossmann A. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogue octreotide. Hormones. 2002;1(3):149–56.

    PubMed  Google Scholar 

  9. Adelstein SJ. The Auger process: a therapeutic promise? AJR. 1993;160:707–13.

    PubMed  CAS  Google Scholar 

  10. Breeman WA, De Jong M, Kwekkeboom DK, Valkema R, Bakker WH, Kooij PPM, et al. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives. Eur J Nucl Med. 2001;28:1421–9.

    Article  PubMed  CAS  Google Scholar 

  11. McLean JR, Wilkinson D. The radiation dose to cells in vitro from intracellular indium-111. Biochem Cell Biol. 1989;67:661–5.

    Article  PubMed  CAS  Google Scholar 

  12. Mariani G, Bodei L, Adelstein SJ, Kassis AI, et al. Emerging roles for radiometabolic therapy of tumours based on auger electron emission. J Nucl Med. 2000;41:1519–21.

    PubMed  CAS  Google Scholar 

  13. Kassis AI, Adelstein SJ. Radiobiologic principles in radionuclide. therapy. J Nucl Med. 2005;46:4S–12S.

    PubMed  Google Scholar 

  14. Wiseman GA, Kvols LK. The radiolabelled MIBG and Somatostatin analogues. Semin Nucl Med 1995;XXV(3):272–8.

    Article  Google Scholar 

  15. De Jong M, Bakker WH, Krenning EP, Breeman WAP, Van der Pluijm ME, Bernard BF, et al. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA, D-Phe1, Tyr3]-octreotide; a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med. 1997;24:368–71.

    Article  PubMed  Google Scholar 

  16. Limouris GS, Lyra M, Skarlos D, Hatziioannou A, Gouliamos A, Moulopoulou A, et al. Auger and conversion electron therapy with In-111 pentetreotide in hepatocellular carcinoma. In: Bergmann H, Koehn H, Sinzinger H, editors. Radioactive isotopes in clinical medicine and research. Boston: Birkhäuser; 1999. p. 551–4.

    Google Scholar 

  17. Valkema R, De Jong M, Bakker WH, Breeman WAP, Kooij PPM, Lugtenburg PJ, et al. Phase I study of peptide receptor radionuclide therapy with [111In-DTPA°]octreotide: the Rotterdam experience. Semin Nucl Med. 2002;32(2):110–22.

    Article  PubMed  Google Scholar 

  18. Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJM, Kooij PPM, De Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA°, Tyr3]octreotate. Eur J Nucl Med. 2003;30:417–22.

    CAS  Google Scholar 

  19. Caplin ME, Mielcarek W, Buscombe JR, Jones AL, Croasdale PL, Cooper MS, et al. Toxicity of high-activity in-111 octreotide therapy in patients with disseminated neuroendocrine tumours. Nucl Med Commun. 2000;21:97–102.

    Article  PubMed  CAS  Google Scholar 

  20. Lafortune M, Madore F, Patriquin H, Breton G. Segmental anatomy of the liver; a US approach to the Couinaud nomenclature. Radiology. 1991;181:443–8.

    PubMed  CAS  Google Scholar 

  21. Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med. 1999;40:37–61.

    Google Scholar 

  22. Kontogeorgakos D, Dimitriou P, Limouris GS, Vlachos LJ. Patient specific dosimetry calculations during therapy with in-111-DTPA-d-Phe1-octreotide infusions after catheterization of the hepatic artery using mathematical models of different anatomical sizes. J Nucl Med. 2006;47(9):1476–82.

    PubMed  CAS  Google Scholar 

  23. Therasse P, Arbuck SG, Eienhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumours. J Natl Cancer Inst. 2000;92(30):205–16.

    Article  PubMed  CAS  Google Scholar 

  24. Stabin M. MIRDOSE: the personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 1996;37:538–46.

    PubMed  CAS  Google Scholar 

  25. Hellman P, Lundström T, Öhrvall V, Eriksson B, Skogseid B, Öberg K, et al. Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases. World J Surg. 2002;26:991–97.

    Article  PubMed  Google Scholar 

  26. Öberg K. Therapeutic alternative in metastasizing neuroendocrine tumours; in carefully selected cases liver transplantation is possible? Laekartidningen. 1999;96:3745–7.

    Google Scholar 

  27. Kress O, Wagner HJ, Wied M, Klose KJ, Arnold R, Alfke H. Transarterial chemoembolization of advanced liver metastases of neuroendocrine tumours; a retrospective single-center analysis. Digestion. 2003;68:94–101.

    Article  PubMed  CAS  Google Scholar 

  28. Dodd GD, Soulen MC, Kane RA, Livraghi T, Lees WR, Yamashita Y, et al. Minimally invasive treatment of malignant hepatic tumours; at the threshold of major breakthrough. Radiographics. 2000;20:9–27.

    PubMed  Google Scholar 

  29. Öberg K. Carcinoid tumours: molecular genetics, tumour biology and update of diagnosis and treatment. Curr Opin Oncol. 2002;14:38–45.

    Article  PubMed  Google Scholar 

  30. Öberg K. Interferon in the management of neuroendocrine GEP-tumours: a review. Digestion 2000;62(Suppl 1):92–7.

    PubMed  Google Scholar 

  31. Kaltsas GA, Besser MG, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25(3):458–511.

    Article  PubMed  CAS  Google Scholar 

  32. Kaltsas GA, Mucherjee JJ, Plowman PN, Grassman AB. The role of chemotherapy in the nonsurgical management of malignant neuroendocrine tumours. Clin Endocrinol. 2001;55:575–87.

    Article  CAS  Google Scholar 

  33. Wang DG. Apoptosis in neuroendocrine tumours. Clin Endocrinol. 1999;51:1–9.

    Article  CAS  Google Scholar 

  34. Virgolini I, Britton K, Buscome JR, Moncay R, Paganelli G, Riva P. In- and Y-DOTA lanreotide: results and implications of the Mauritius trial. Semin Nucl Med. 2000;32:148–55.

    Article  Google Scholar 

  35. Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, et al. Receptor-mediated radiotherapy with Y-90-d-Phe1-Tyr3-octreotide. Eur J Nucl Med. 2001;28:426–34.

    Article  PubMed  CAS  Google Scholar 

  36. Handkiewicz Junak D, Baum R, Jarzab B. Leukocyte and white blood cell toxicity during long-term peptide receptor radiotherapy using Y-90 and Lu-177 labelled somatostatin analogues. Eur J Nucl Med 2005;32(9):S100.

    Google Scholar 

  37. Kwekkeboom DJ, Bakker WH, Kooij PPM, Konijnenberg MW, Srinivasan A, Erion JL, et al. Lu-177-DOTA Tyr octreotate: comparison with In-111-DTPA-octreotide in patients. Eur J Nucl Med. 2001;28:1319–25.

    Article  PubMed  CAS  Google Scholar 

  38. Anthony LB, Woltering EA, Espanan GD, Cronin MD, Maloney TJ, McCarthy KE, et al. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med. 2002;32(2):123–32.

    Article  PubMed  Google Scholar 

  39. Buscombe JR, Caplin ME, Hilson JW. Long-term efficacy of high-activity 111In-pentetreotide therapy in patients with disseminated neuroendocrine tumors. J Nucl Med. 2003;44:1–6.

    PubMed  CAS  Google Scholar 

  40. Förster GJ, Engelbach M, Brockmann J, Reber H, Buchholz H-G, Mäcke HR, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  41. Helisch A, Förster GJ, Reber H, Buchholz H-G, Arnold R, Göke B, et al. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31(10):1386–92.

    Article  PubMed  CAS  Google Scholar 

  42. Goddu SM, Budinger TF. MIRD: cellular S values. Reston, VA: SNM; 1997.

    Google Scholar 

  43. Buchegger F, Perillo-Adamer F, Dupertuis YM, Bischof Delaloye A. Auger radiation targeted into DNA: a therapy perspective. Eur J Nucl Med Mol Imaging. 2006;33(11):1352–63.

    Article  PubMed  Google Scholar 

  44. Health Physics J. RADAR; 2008. http://www.doseinfo-radar.com/RADARSoft.html

  45. Limouris GS, Dimitropoulos N, Kontogeorgakos D, Papanikolos G, Koutoulidis V, Hatzioannou A, et al. Evaluation of the therapeutic response to In-111-DTPA octreotide-based targeted therapy in liver metastatic neuroendocrine tumours according to CT/MRI/US findings. Cancer Biother Radiopharm. 2005;20(2):215–7.

    Article  PubMed  CAS  Google Scholar 

  46. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nuclear Med. 2005;46(Suppl 1):62–6.

    Google Scholar 

  47. 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. 2003;30:207–16.

    CAS  Google Scholar 

  48. 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 90Y-DOTATOC. J Nucl Med. 2002;43(5):610–6.

    PubMed  CAS  Google Scholar 

  49. Cremonesi M, Ferrari M, Bodei L, Tosi G, Paganelli G. Dosimetry in peptide radionuclide receptor therapy: a review. J Nucl Med. 2006;47(9):1467–75.

    PubMed  CAS  Google Scholar 

  50. De Jong M, Valkema R, Van Gameren A, Van Boven H, Bex A, Van de Weyer EP, et al. Inhomogenous localization of radioactivity in the human kidney after injection of [111In-DTPA]octreotide. J Nucl Med. 2004;45(7):1168–71.

    PubMed  Google Scholar 

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Acknowledgement

This project was co-financed within Op. Education by the ESF (European Social Fund) and National Resources (Irakleitos program grants 70/3/7166 and 70/3/7231). We are thankful to Maria Paphiti, radiation physicist, for her valuable assistance.

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Authors and Affiliations

  1. Divisions of Nuclear Medicine, Radiology I Department, Aretaieion University Hospital, Athens Medical School, Athens, Greece

    Georgios S. Limouris, Dimitrios Kontogeorgakos, Maria Lyra, Panagiotis Dimitriou & Anastasia Stavraka

  2. Divisions of Angiography, Radiology I Department, Aretaieion University Hospital, Athens Medical School, Athens, Greece

    Achilles Chatziioannou, Dimitrios Mourikis, Athanassios Gouliamos & Lambros Vlahos

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  1. Georgios S. Limouris
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Correspondence to Georgios S. Limouris.

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Limouris, G.S., Chatziioannou, A., Kontogeorgakos, D. et al. Selective hepatic arterial infusion of In-111-DTPA-Phe1-octreotide in neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging 35, 1827–1837 (2008). https://doi.org/10.1007/s00259-008-0779-0

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