Dosimetry for Peptide Receptor Radionuclide Therapy

  • Marta Cremonesi
  • Christiane Schuchardt
Part of the Medical Radiology book series (MEDRAD)


For over more than a decade, the progressive evolution of Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of tumors expressing somatostatin receptors has been constantly challenging—and challenged by—dosimetry. The improvements reached in the therapeutical applications of 90Y- and 177Lu- radiolabeled peptides are considerable, and new perspectives are on the way. These results have been possible due to the special complicity among various disciplines having the optimization of PPRT as common goal, with dosimetry at center stage. Its role has been precious for an attentive radionuclide and radiopeptide selection, for the upgrading of the protocol rationales and therapy schemes, for toxicity prevention. Especially, the high irradiation of the kidneys, the low but inevitable dose to the bone marrow, as well as the large dose variability of non-target organs and tumors, which emerged from the clinical trials, have been sustaining the need of reliable dosimetry. Although dose estimates still do not reach the finest accuracy, relevant progress in dosimetric methods is being obtained. Their application to this quite early therapy—avid of information—addresses the examination of the risk-benefit balance, toward the approach of a tailored treatment planning. The availability of dosimetric data has allowed to evaluate the efficacy of renal protective agents and to validate radiobiological models for dose-toxicity correlations on kidneys. The probability of renal impairment being predictable, the injected activity can be fitted to any patient for a safe kidney dose.


External Beam Radiation Therapy Peptide Receptor Radionuclide Therapy Dose Volume Histogram Biological Effective Dose Equivalent Uniform Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors wish to thank Mrs Deborah Console for editing the manuscript, Dr. Stefano Papi for useful discussions on radiochemical analyses, and the colleagues of the Medical Physics and Nuclear Medicine Divisions for their support.


  1. Baechlera S, Hobbs RF, Prideaux AR et al (2008) Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry. Med Phys 35:1123–1134CrossRefGoogle Scholar
  2. Barone R, Borson-Chazot F, Valkema R et al. (2005) Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose–effect relationship. J Nucl Med 46 (supp):99S–106SGoogle Scholar
  3. Bodei L, Cremonesi M, Zoboli S et al (2003) Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med 30:207–216CrossRefGoogle Scholar
  4. Bodei L, Cremonesi M, Grana C et al (2004) Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 31:1038–1046PubMedCrossRefGoogle Scholar
  5. Bodei L, Cremonesi M, Ferrari M et al (2008) Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with (90)Y-DOTATOC and (177) Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 35:1847–1856PubMedCrossRefGoogle Scholar
  6. Bodei L, Ferone D, Grana CM et al (2009) Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 32:360–369PubMedCrossRefGoogle Scholar
  7. Botta F, Valente M, Di Dia A et al (2008) 3D absorbed dose distribution inside and outside 90Y, 177Lu and 131I sources of spherical shape by Monte Carlo simulation with the PENELOPE algorithm [abstract]. Eur J Nucl Med Mol Imaging 35:S201Google Scholar
  8. Bouchet LG, Bolch WE, Blanco HP et al (2003) MIRD Pamphlet No 19: absorbed fractions and radionuclide S values for six age-dependent multiregion models of the kidney. J Nucl Med 44:1113–1147PubMedGoogle Scholar
  9. Breeman WA, van der Wansem K, Bernard BF et al (2003a) The addition of DTPA to [177Lu-DOTA0, Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. Eur J Nucl Med Mol Imaging 30(2):312–315PubMedCrossRefGoogle Scholar
  10. Breeman WA, de Jong M, Visser TJ et al (2003b) Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging 30(6):917–920PubMedCrossRefGoogle Scholar
  11. Cassady JR (1995) Clinical radiation nephropathy. Int J Radiat Oncol Biol Phys 30, 31(5):1249–1256Google Scholar
  12. Cremonesi M, Ferrari M, Bodei L et al (2006a) Dosimetry in Peptide radionuclide receptor therapy: a review. J Nucl Med 47(9):1467–1475PubMedGoogle Scholar
  13. Cremonesi M, Ferrari M, Bodei L et al (2006b) Dosimetry in patients undergoing 177Lu-DOTATATE therapy with indications for 90Y- DOTATATE [abstract]. Eur J Nucl Med Mol Imaging 33:S102CrossRefGoogle Scholar
  14. Cremonesi M, Bodei L, Botta F et al (2009) Time interval, number of cycles and radionuclide choice in PRRT (Peptide Receptor Radionuclide Therapy): radiobiological considerations to guide therapy planning [abstract]. Eur J Nucl Med Mol Imaging 36:S194Google Scholar
  15. Cremonesi M, Botta F, Di Dia A et al (2010) Dosimetric approaches dosimetry for treatment with radiolabelled somatostatin analogues: a review. Q J Nucl Med Mol Imaging 54(1):37–51PubMedGoogle Scholar
  16. Dale RG (1996) Dose-rate effects in targeted radiotherapy. Phys Med Biol 41:1871–1884PubMedCrossRefGoogle Scholar
  17. de Jong M, Breeman WA, Valkema R et al (2005) Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs [abstract]. J Nucl Med 46(suppl):13S–17SPubMedGoogle Scholar
  18. Dewaraja YK, Frey EC, Sgouros G et al (2012) MIRD Pamphlet No. 23: Quantitative SPECT for Patient-Specific 3-Dimensional Dosimetry in Internal Radionuclide Therapy. J Nucl Med 53:1310-1325PubMedCentralPubMedCrossRefGoogle Scholar
  19. Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122PubMedCrossRefGoogle Scholar
  20. Esser JP, Krenning EP, Teunissen JJ et al (2006) Comparison of [(177)Lu-DOTA(0), Tyr(3)] octreotate and [(177)Lu-DOTA(0), Tyr(3)] octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging 33(11):1346–1351PubMedCrossRefGoogle Scholar
  21. Forrer F, Uusijärvi H, Waldherr C et al (2004) 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 31:1257–1262PubMedCrossRefGoogle Scholar
  22. Forrer F, Krenning EP, Kooij PP et al (2009) Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0), Tyr(3)] octreotate. Eur J Nucl Med Mol Imaging 36(7):1138–1146PubMedCentralPubMedCrossRefGoogle Scholar
  23. Forster GJ, Engelbach MJ, Brockmann JJ et al (2001) 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 28:1743–1750PubMedCrossRefGoogle Scholar
  24. Garkavij M, Nickel M, Sjögreen-Gleisner K et al. (2010) (177)Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer 16(S4):1084–1092Google Scholar
  25. Helisch A, Förster GJ, Reber H et al (2004) Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe 1-Tyr 3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 31:1386–1392PubMedCrossRefGoogle Scholar
  26. Hindorf C, Chittenden S, Causer L et al (2007) Dosimetry for (90)Y-DOTATOC therapies in patients with neuroendocrine tumors. Cancer Biother Radiopharm 22:130–135PubMedCrossRefGoogle Scholar
  27. International Commission on Radiological Protection (1979) Limits for intakes of radionuclides by workers. ICRP Publication 30. Pergamon Press, New YorkGoogle Scholar
  28. Jamar F, Barone R, Mathieu I et al (2003) 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 30:510–518PubMedCrossRefGoogle Scholar
  29. Kalogianni E, Flux GD, Malaroda A (2007) The use of BED and EUD concepts in heterogeneous radioactivity distributions on a multicellular scale for targeted radionuclide therapy. Cancer Biother Radiopharm 22:143–150PubMedCrossRefGoogle Scholar
  30. Konijnenberg M, Melis M, Valkema R et al (2007) Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy. J Nucl Med 48:134–142PubMedGoogle Scholar
  31. Kunikowska J, Krolicki L, Hubalewska-Dydejczyk A et al (2009) Comparison between clinical results of PRRT with 90Y-DOTATATE and 90Y/177Lu-DOTATATE [abstract]. Eur J Nucl Med Mol Imaging 36:S194Google Scholar
  32. Kwekkeboom DJ, Kooij PP, Bakker WH et al (1999) Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med 40:762–767PubMedGoogle Scholar
  33. Kwekkeboom DJ, Bakker WH, Kooij PP et al (2001) [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med 28(9):1319–1325PubMedCrossRefGoogle Scholar
  34. Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130PubMedCrossRefGoogle Scholar
  35. Loevinger R, Budinger T, Watson EE (1991) MIRD Primer for absorbed dose calculations. The Society of Nuclear Medicine, New YorkGoogle Scholar
  36. Minarik D, Sjögreen Gleisner K, Ljungberg M (2008) Evaluation of quantitative (90)Y SPECT based on experimental phantom studies. Phys Med Biol 53:5689–5703PubMedCrossRefGoogle Scholar
  37. Minarik D, Ljungberg M, Segars P, Gleisner KS et al (2009) Evaluation of quantitative planar 90Y bremsstrahlung whole-body imaging. Phys Med Biol 54:5873–5883PubMedCrossRefGoogle Scholar
  38. O’Donoghue JA (1999) Implications of nonuniform tumor doses for radioimmunotherapy. J Nucl Med 40:1337–1341PubMedGoogle Scholar
  39. Pentlow KS, Finn RD, Larson SM et al (2000) Quantitative imaging of Yttrium-86 with PET. the occurrence and correction of anomalous apparent activity in high density regions. Clin Positron Imaging 3(3):85–90PubMedCrossRefGoogle Scholar
  40. Prideaux AR, Song H, Hobbs RF et al (2007) Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling to patient-specific 3-dimensional imaging-based internal dosimetry. J Nucl Med 48(6):1008–1016PubMedCentralPubMedCrossRefGoogle Scholar
  41. Rodrigues M, Traub-Weidinger T, Li S et al (2006) Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 33:532–540PubMedCrossRefGoogle Scholar
  42. Rolleman EJ, Melis M, Valkema R et al (2010) Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. Eur J Nucl Med Mol Imaging 37:1018–1031PubMedCrossRefGoogle Scholar
  43. Sandström M, Garske U, Granberg D et al (2010) Individualized dosimetry in patients undergoing therapy with 177Lu-DOTA-D-Phe1-Tyr3-octreotate. Eur J Nucl Med Mol Imaging 37(2):212–225PubMedCrossRefGoogle Scholar
  44. Siegel JA, Thomas SR, Stubbs JB et al (1999) Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. MIRD Pamphlet No.16. J Nucl Med 40:S37–S61Google Scholar
  45. Sjögreen K, Ljungberg M, Wingårdh K et al (2005) The LundADose method for planar image activity quantification and absorbed-dose assessment in radionuclide therapy. Cancer Biother Radiopharm 20:92–97PubMedCrossRefGoogle Scholar
  46. Stabin MG (2008) Uncertainties in internal dose calculations for radiopharmaceuticals. J Nucl Med 49:853–860PubMedCrossRefGoogle Scholar
  47. Stabin MG (2010) From the RADAR task group. J Nucl Med 51:13N, 26N.
  48. Stabin MG, Sparks RB, Crowe E (2005) OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 46:1023–1027PubMedGoogle Scholar
  49. Svensson J, Molne J, Schmitt A et al (2009) Equal mean absorbed kidney dose from 177Lu-DOTATATE will generate different kidney toxicity profiles in nude mice. Eur J Nucl Med Mol Imaging 36 (supp):S206Google Scholar
  50. van Essen M, Krenning EP, Kam BL et al (2009) Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 5(7):382–393PubMedGoogle Scholar
  51. Walrand S, Flux GD, Konijnenberg MW et al (2011) Dosimetry of yttrium-labelled radiopharmaceuticals for internal therapy: 86Y or 90Y imaging? Eur J Nucl Med Mol Imaging 38(Suppl 1):S57–S68Google Scholar
  52. Wehrmann C, Senftleben S, Zachert C et al (2007) Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm 22:406–416PubMedCrossRefGoogle Scholar
  53. Wessels BW, Konijnenberg MW, Dale RG et al (2008) MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response–implications for radionuclide therapy. J Nucl Med 49:1884–1899PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg  2012

Authors and Affiliations

  1. 1.Deputy Director, Medical PhysicsIstituto Europeo di OncologiaMilanoItaly

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