Dosimetry in PRRT

  • Marta Cremonesi
  • Mahila Ferrari
  • Francesca Botta


Peptide receptor radionuclide therapy (PRRT) with 90Y- and 177Lu-radiolabelled peptides represents a promising option for patients with somatostatin receptor-expressing tumours. Several clinical trials have proven its efficacy and a general profile of low toxicity. Although in a minority of patients, severe events of kidney toxicity have occurred, so the kidneys represent the organ at risk, especially for 90Y-peptides, followed by red marrow, as also haematological toxicity, rarely at high grade, may occur in both 90Y- and 177Lu-PRRT. The results of some studies have shown important dose-effect correlations, especially for renal damage, showing the possibility not only to avoid unwanted effects when absorbed dose prescriptions are respected but also to optimise therapy. However, due to the large variability of biokinetics among patients, individual dosimetry is necessary for tailored PRRT.

The following chapter summarises the methods for PRRT dosimetry and the major dosimetric and radiobiological results present in the literature, highlighting correlations and challenging perspectives. Possible approaches for simplified dosimetry are also described.


Dosimetry in PRRT Kidney dosimetry 90Y-PRRT and 177Lu-PRRT Dose-effect correlations 


  1. 1.
    Bodei L, Cremonesi M, Kidd M, et al. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors. Thorac Surg Clin. 2014;24(3):333–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–35.PubMedCrossRefGoogle Scholar
  3. 3.
    van Essen M, Krenning EP, Kam BL, et al. Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol. 2009;5:382–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Baechler S, Hobbs RF, Prideaux AR, et al. Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry. Med Phys. 2008;35:1123–34.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Barone R, Borson-Chazot F, Valkema R, et al. Patient-specific dosimetry in predicting renal toxicity with (90)Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship. J Nucl Med. 2005;46(Suppl 1):99S–106S.PubMedGoogle Scholar
  6. 6.
    Dale R. Use of the linear-quadratic radiobiological model for quantifying kidney response in targeted radiotherapy. Cancer Biother Radiopharm. 2004;19:363–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Garkavij M, Nickel M, Sjogreen-Gleisner K, et al. 177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer. 2010;116:1084–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Gustafsson J, Brolin G, Cox M, et al. Uncertainty propagation for SPECT/CT-based renal dosimetry in (177)Lu peptide receptor radionuclide therapy. Phys Med Biol. 2015;60(21):8329–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Ilan E, Sandström M, Wassberg C, et al. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE. J Nucl Med. 2015;56(2):177–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Larsson M, Bernhardt P, Svensson JB, et al. Estimation of absorbed dose to the kidneys in patients after treatment with 177Lu-octreotate: comparison between methods based on planar scintigraphy. EJNMMI Res. 2012;2:49.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Lassmann M, Chiesa C, Flux G, et al. EANM dosimetry committee guidance document: good practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging. 2011;38(1):192–200.PubMedCrossRefGoogle Scholar
  12. 12.
    Ljungberg M, Celler A, Konijnenberg MW, et al. MIRD pamphlet no. 26: joint EANM/MIRD guidelines for quantitative 177Lu SPECT applied for dosimetry of radiopharmaceutical therapy. J Nucl Med. 2016;57(1):151–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Sandstrom M, Garske-Roman U, Granberg D, et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. J Nucl Med. 2013;54:33–41.PubMedCrossRefGoogle Scholar
  14. 14.
    Sandström M, Ilan E, Karlberg A, et al. Method dependence, observer variability and kidney volumes in radiation dosimetry of (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours. EJNMMI Phys. 2015;2(1):24.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Strigari L, Benassi M, Chiesa C, et al. Dosimetry in nuclear medicine therapy: radiobiology application and results. Q J Nucl Med Mol Imaging. 2011;55(2):205–21.PubMedGoogle Scholar
  16. 16.
    Strigari L, Konijnenberg M, Chiesa C, et al. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy. Eur J Nucl Med Mol Imaging. 2014;41(10):1976–88.PubMedCrossRefGoogle Scholar
  17. 17.
    Swärd C, Bernhardt P, Ahlman H, et al. [177Lu-DOTA 0-Tyr 3]-octreotate treatment in patients with disseminated gastroenteropancreatic neuroendocrine tumors: the value of measuring absorbed dose to the kidney. World J Surg. 2010;34(6):1368–72.PubMedCrossRefGoogle Scholar
  18. 18.
    Wessels BW, Konijnenberg MW, Dale RG, et al. MIRD pamphlet no. 20: the effect of model assumptions on kidney dosimetry and response--implications for radionuclide therapy. J Nucl Med. 2008;49:1884–99.PubMedCrossRefGoogle Scholar
  19. 19.
    Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30.PubMedCrossRefGoogle Scholar
  20. 20.
    Eberlein U, Cremonesi M, Lassmann M. Individualized dosimetry for theranostics: necessary, nice to have, counterproductive? J Nucl Med. 2017;58(Suppl 2):97S–103S.PubMedCrossRefGoogle Scholar
  21. 21.
    Van Binnebeek S, Baete K, Vanbilloen B, et al. Individualized dosimetry-based activity reduction of 90Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2014;41:1141–57.PubMedGoogle Scholar
  22. 22.
    Fabbri C, Sarti G, Cremonesi M, et al. Quantitative analysis of 90Y bremsstrahlung SPECT-CT images for application to 3D patient-specific dosimetry. Cancer Biother Radiopharm. 2009;24:145–54.PubMedCrossRefGoogle Scholar
  23. 23.
    Minarik D, Sjögreen Gleisner K, Ljungberg M. Evaluation of quantitative (90)Y SPECT based on experimental phantom studies. Phys Med Biol. 2008;53:5689–703.PubMedCrossRefGoogle Scholar
  24. 24.
    Minarik D, Ljungberg M, Segars P, Gleisner KS. Evaluation of quantitative planar 90Y bremsstrahlung whole-body imaging. Phys Med Biol. 2009;54:5873–83.PubMedCrossRefGoogle Scholar
  25. 25.
    Fabbri C, Bartolomei M, Mattone V, et al. (90)Y-PET/CT imaging quantification for dosimetry in peptide receptor radionuclide therapy: analysis and corrections of the impairing factors. Cancer Biother Radiopharm. 2015;30(5):200–10.PubMedCrossRefGoogle Scholar
  26. 26.
    Martí-Climent JM, Prieto E, Elosúa C, et al. PET optimization for improved assessment and accurate quantification of 90Y-microsphere biodistribution after radioembolization. Med Phys. 2014;41(9):092503.PubMedCrossRefGoogle Scholar
  27. 27.
    Willowson KP, Tapner M, QUEST Investigator Team, et al. A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres: the QUEST phantom study. Eur J Nucl Med Mol Imaging. 2015;42(8):1202–22.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Cremonesi M, Botta F, Di Dia A, et al. Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging. 2010;54:37–51.PubMedGoogle Scholar
  29. 29.
    Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46(6):1023–7.PubMedGoogle Scholar
  30. 30.
    Bolch WE, Eckerman KF, Sgouros G, et al. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry--standardization of nomenclature. J Nucl Med. 2009;50(3):477–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Cremonesi M, Ferrari M, Bodei L, et al. Dosimetry in patients undergoing 177Lu-DOTATATE therapy with indications for 90Y- DOTATATE. Eur J Nucl Med Mol Imaging. 2006;33:S102.CrossRefGoogle Scholar
  32. 32.
    Guerriero F, Ferrari ME, Botta F, et al. Kidney dosimetry in 177Lu and 90Y peptide receptor radionuclide therapy: influence of image timing, time-activity integration method, and risk factors. Biomed Res Int. 2013;2013:935351.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Siegel JA, Thomas SR, Stubbs JB, 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;40:37S–61S.PubMedGoogle Scholar
  34. 34.
    Cremonesi M, Ferrari M, Zoboli S, et al. Biokinetics and dosimetry in patients administered with (111)in-DOTA-Tyr(3)-octreotide: implications for internal radiotherapy with (90)Y-DOTATOC. Eur J Nucl Med. 1999;26:877–86.PubMedCrossRefGoogle Scholar
  35. 35.
    Ljungberg M, Gleisner KS. Hybrid imaging for patient-specific dosimetry in radionuclide therapy. Diagnostics. 2015;5(3):296–317.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Bodei L, Kidd M, Modlin IM, et al. Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status. Eur J Nucl Med Mol Imaging. 2015;42(9):1341–52.PubMedCrossRefGoogle Scholar
  37. 37.
    Forrer F, Krenning EP, Kooij PP, et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0),Tyr(3)]octreotate. Eur J Nucl Med Mol Imaging. 2009;36:1138–46.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Valkema R, Pauwels S, Kvols LK, 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;36:147–56.PubMedCrossRefGoogle Scholar
  39. 39.
    Bodei L, Mueller-Brand J, Baum RP, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40:800–16.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Rolleman EJ, Melis M, Valkema R, et al. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. Eur J Nucl Med Mol Imaging. 2010;37(5):1018–31.PubMedCrossRefGoogle Scholar
  41. 41.
    Sandström M, Garske U, Granberg D, et al. Individualized dosimetry in patients undergoing therapy with (177)Lu-DOTA-D-Phe (1)-Tyr (3)-octreotate. Eur J Nucl Med Mol Imaging. 2010;37:212–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Bodei L, Cremonesi M, Ferrari 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med. 2001;28(10):1552–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Sarnelli A, Guerriero F, Botta F, et al. Therapeutic schemes in177Lu and 90Y-PRRT: radiobiological considerations. Q J Nucl Med Mol Imaging. 2017;61(2):216–31.PubMedGoogle Scholar
  45. 45.
    Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedCrossRefGoogle Scholar
  46. 46.
    Baechler S, Hobbs RF, Boubaker A, et al. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy. Med Phys. 2012;39(10):6118–28.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Imhof A, Brunner P, Marincek N, 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.PubMedCrossRefGoogle Scholar
  48. 48.
    Otte A, Weiner SM, Cybulla M. Is radiation nephropathy caused by yttrium-90? Lancet. 2002;359(9310):979.PubMedCrossRefGoogle Scholar
  49. 49.
    Bergsma H, Konijnenberg MW, Kam BL, et al. Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic factors, incidence and course. Eur J Nucl Med Mol Imaging. 2016;43(3):453–63.PubMedCrossRefGoogle Scholar
  50. 50.
    Konijnenberg M, Melis M, Valkema R, et al. Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy. J Nucl Med. 2007;48:134–42.PubMedGoogle Scholar
  51. 51.
    Bouchet LG, Bolch WE, Blanco HP, et al. MIRD pamphlet no 19: absorbed fractions and radionuclide S values for six age-dependent multiregion models of the kidney. J Nucl Med. 2003;44(7):1113–47.PubMedGoogle Scholar
  52. 52.
    Green A, Flynn A, Pedley RB, et al. Nonuniform absorbed dose distribution in the kidney: the influence of organ architecture. Cancer Biother Radiopharm. 2004;19:371–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Pauwels S, Barone R, Walrand S, et al. Practical dosimetry of peptide receptor radionuclide therapy with (90)Y-labeled somatostatin analogs. J Nucl Med. 2005;46:92S–8S.PubMedGoogle Scholar
  54. 54.
    Bergsma H, Konijnenberg MW, van der Zwan WA, et al. Nephrotoxicity after PRRT with (177)Lu-DOTA-octreotate. Eur J Nucl Med Mol Imaging. 2016;43(10):1802–11.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, et al. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38(10):1788–97.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Seregni E, Maccauro M, Chiesa C, et al. Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy. Eur J Nucl Med Mol Imaging. 2014;41(2):223–30.PubMedCrossRefGoogle Scholar
  57. 57.
    Hänscheid H, Lapa C, Buck AK, et al. Dose mapping after endoradiotherapy with 177Lu-DOTATATE/−TOC by one single measurement after four days. J Nucl Med. 2017.
  58. 58.
    Bodei L, Kidd M, Paganelli G, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015b;42(1):5–19.PubMedCrossRefGoogle Scholar
  59. 59.
    Bodei L, Kidd M, Modlin IM, et al. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2016;43(5):839–51.PubMedCrossRefGoogle Scholar
  60. 60.
    Bodei L, Cremonesi M, Grana CM, et al. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011;38(12):2125–35.PubMedCrossRefGoogle Scholar
  61. 61.
    Claringbold PG, Brayshaw PA, Price RA, et al. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38(2):302–11.PubMedCrossRefGoogle Scholar
  62. 62.
    Forrer F, Uusijarvi H, Waldherr C, et al. A comparison of (111)In-DOTATOC and (111)In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1257–62.PubMedCrossRefGoogle Scholar
  63. 63.
    Forster GJ, Engelbach MJ, Brockmann JJ, 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.PubMedCrossRefGoogle Scholar
  64. 64.
    Gupta SK, Singla S, Thakral P, et al. Dosimetric analyses of kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors of patients treated with 177Lu-DOTATATE. Clin Nucl Med. 2013;38:188–94.PubMedCrossRefGoogle Scholar
  65. 65.
    Helisch A, Forster GJ, Reber H, 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;31:1386–92.PubMedCrossRefGoogle Scholar
  66. 66.
    Hindorf C, Chittenden S, Causer L, et al. Dosimetry for (90)Y-DOTATOC therapies in patients with neuroendocrine tumors. Cancer Biother Radiopharm. 2007;22:130–5.PubMedCrossRefGoogle Scholar
  67. 67.
    Jamar F, Barone R, Mathieu I, 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.PubMedCrossRefGoogle Scholar
  68. 68.
    Kairemo K, Kangasmaki A. 4D SPECT/CT acquisition for 3D dose calculation and dose planning in (177)Lu-peptide receptor radionuclide therapy: applications for clinical routine. Recent Results Cancer Res. 2013;194:537–50.PubMedCrossRefGoogle Scholar
  69. 69.
    Kwekkeboom DJ, Kooij PP, Bakker WH, et al. Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med. 1999;40:762–7.PubMedGoogle Scholar
  70. 70.
    Kwekkeboom DJ, Bakker WH, Kooij PP, et al. [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med. 2001;28(9):1319–25.PubMedCrossRefGoogle Scholar
  71. 71.
    Rodrigues M, Traub-Weidinger T, Li S, et al. 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. 2006;33:532–40.PubMedCrossRefGoogle Scholar
  72. 72.
    Wehrmann C, Senftleben S, Zachert C, et al. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm. 2007;22:406–16.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marta Cremonesi
    • 1
  • Mahila Ferrari
    • 1
  • Francesca Botta
    • 1
  1. 1.Istituto Europeo di OncologiaMilanItaly

Personalised recommendations