4D SPECT/CT Acquisition for 3D Dose Calculation and Dose Planning in 177Lu-Peptide Receptor Radionuclide Therapy: Applications for Clinical Routine

  • Kalevi Kairemo
  • Aki Kangasmäki
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 194)


Molecular radiotherapy combines the potential of a specific tracer (vector) targeting tumor cells with local radiotoxicity. Designing a specific tumor-targeting/killing combination is a tailoring process. Radionuclides with imaging capacity serve best in the selection of the targeting molecule. The potential of targeted therapy with radiolabeled peptides has been reported in many conditions; peptide receptor radionuclide therapy (PRRT) is already part of Scandinavian guidelines for treating neuroendocrine tumors. Lu-177- and Y-90-labeled somatostatin analogs, including DOTATOC, DOTANOC, and DOTATATE, are most the commonly used and have turned out to be effective. For routine use, an efficient, rapid, and reliable dose calculation tool is needed. In this chapter we describe how serial pre- and posttherapeutic scans can be used for dose calculation and for predicting therapy doses. Our software for radionuclide dose calculation is a three-dimensional, voxel-based system. The 3D dose calculation requires coregistered SPECT image sets from several time points after infusion to reconstruct time-activity curves for each voxel. Image registration is done directly by SPECT image registration using the first time point as a target. From the time-activity curves, initial activity and total half-life maps are calculated to produce a cumulated activity map. The cumulated activity map is then convoluted with a voxel-dose kernel to obtain a 3D dose map. We performed dose calculations similarly for both therapeutic and preplanning images. Preplanning dose was extrapolated to predict therapy dose using the ratio of administered activities. Our 3D dose calculation results are also compared with those of OLINDA. Our preliminary results indicate that dose planning using pretherapeutic scanning can predict critical organ and tumor doses. In some cases, the dose planning prediction resulted in slight, and slightly dose-dependent, overestimation of final therapy dose. Real tumor dose was similar in both pretherapeutic and posttherapeutic scans using our software. The OLINDA software and our program gave similar normal organ doses, whereas tumor doses could be calculated in a more detailed manner using the 3D program.


Single Photon Emission Compute Tomography Dose Calculation Single Photon Emission Compute Tomography Image Peptide Receptor Radionuclide Therapy Radionuclide Therapy 
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  1. Bakker WH, Breeman WA, Kwekkeboom DJ et al (2006) Practical aspects of peptide receptor radionuclide therapy with [177Lu][DOTA0, Tyr3]octreotate. Q J Nucl Med Mol Imaging 50:265–271PubMedGoogle Scholar
  2. Bodei L, Cremonesi M, Ferrari M et al (2008) 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 35:1847–1856PubMedCrossRefGoogle Scholar
  3. Bodei L, Cremonesi M, Grana CM et al (2011) Peptide receptor radionuclide therapy with (177)Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging 38(12):2125–2135 epub Sept 3PubMedCrossRefGoogle Scholar
  4. Cremonesi M, Ferrari M, Bodei L et al (2006) Dosimetry in peptide radionuclide receptor therapy: a review. J Nucl Med 47:1467–1475PubMedGoogle Scholar
  5. Cremonesi M, Ferrari M, Di Dia A et al (2011) Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy. Q J Nucl Med Mol Imaging 55:155–167PubMedGoogle Scholar
  6. De Jong M, Valkema R, Van Gameren A et al (2004) Inhomogeneous localization of radioactivity in the human kidney after injection of [(111)In-DTPA]octreotide. J Nucl Med 45:1168–1171PubMedGoogle Scholar
  7. 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 36:1138–1146PubMedCrossRefGoogle Scholar
  8. Gabriel M, Andergassen U, Putzer D et al (2010) Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients. Q J Nucl Med Mol Imaging 54:92–9PubMedGoogle Scholar
  9. Heiskanen T, Heiskanen T, Kairemo K (2009) Development of a PBPK model for monoclonal antibodies and simulation of human and mice PBPK of a radiolabelled monoclonal antibody. Curr Pharm Des 15:988–1007PubMedCrossRefGoogle Scholar
  10. Kairemo K, Lubberink M, Garske U et al (2002) Dosimetry of repeated Y-90-octreotide therapy of somatostatin expressing tumours. World J Nucl Med 1:S134–5Google Scholar
  11. Kangasmäki A, Kiljunen T, Pyyry J et al (2012) A simple individualized 3D dose calculation for radionuclide therapy—applied in 177Lu-DOTA receiving patients. (Submitted)Google Scholar
  12. Konijnenberg M, Bijster M, Krenning EP et al (2004) A stylized computational model of the rat for organ dosimetry in support of preclinical evaluations of peptide receptor radionuclide therapy with 90Y, 111In, or 177Lu. J Nucl Med 45:1260–9PubMedGoogle Scholar
  13. 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
  14. Kwekkeboom DJ, Teunissen JJ, Bakker WH et al (2005) Radiolabeled somatostatin analog 177Lu-DOTA0, Tyr3) octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 23:2754–2762PubMedCrossRefGoogle Scholar
  15. Lubberink M, Garske U, Sandström M et al (2002) Dosimetry of repeated Y-90-SMT 487 (Octreother) therapy of somatostatin expressing tumours using Y-90-bremsstrahlung and In-111-octreotide measurements. Eur J Nucl Med 29:S358Google Scholar
  16. Melis M, Krenning EP, Bernard BF et al (2005) Localisation and mechanism of renal retention of radiolabelled somatostatin analogues. Eur J Nucl Med Mol Imaging 32:1136–1143PubMedCrossRefGoogle Scholar
  17. Pauwels S, Barone R, Walrand S et al (2005) Practical dosimetry of peptide receptor radionuclide therapy with (90)Y-labeled somatostatin analogs. J Nucl Med 46(Suppl 1):92S–8SPubMedGoogle Scholar
  18. Seregni E, Maccauro M, Coliva A et al (2010) Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results. Q J Nucl Med Mol Imaging 54:84–91PubMedGoogle Scholar
  19. Siegel JA, Stabin MG, Sharkey RM (2010) Renal dosimetry in peptide radionuclide receptor therapy. Cancer Biother Radiopharm 25:581–8PubMedCrossRefGoogle Scholar
  20. Tiensuu Janson E, Sorbye H, Welin S et al (2010) Nordic guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors. Acta Oncol 49:740–756CrossRefGoogle Scholar
  21. van Eerd JE, Vegt E, Wetzels JF et al (2006) Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J Nucl Med 47:528–533PubMedGoogle Scholar
  22. Vegt E, Wetzels JF, Russel FG et al (2006) Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin. J Nucl Med 47:432–6PubMedGoogle Scholar
  23. 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
  24. 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 2013

Authors and Affiliations

  1. 1.Departments of Nuclear Medicine, Molecular Radiotherapy and Medical PhysicsDocrates International Comprehensive Cancer CenterHelsinkiFinland

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