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Der Nuklearmediziner 2018; 41(01): 69-80
DOI: 10.1055/s-0043-122171
Dosimetrie
© Georg Thieme Verlag KG Stuttgart · New York

Dosimetrie bei der Radionuklidtherapie mit Lu-177

Dosimetry for Radionuclide Therapy using Lu-177
Astrid Gosewisch
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, LMU München, München
,
Harun Ilhan
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, LMU München, München
,
Lena Vomacka
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, LMU München, München
,
Guido Böning
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, LMU München, München
› Author Affiliations
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Publication History

Publication Date:
01 March 2018 (online)

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Zusammenfassung

Die Radioligandentherapie (RLT) mit radioaktiv markierten PSMA-Liganden (z. B. Lu-177-PSMA-617) und die Peptid-Rezeptor-Radionuklidtherapie (PRRT) mit radioaktiv markierten Somatostatin-Analoga (z. B. Lu-177-DOTATATE) haben sich über die letzten Jahre als vielversprechende Therapieoptionen bei metastasierten, kastrationsresistenten Prostatakarzinomen bzw. inoperablen oder metastasierten neuroendokrinen Tumoren entwickelt. Das Theragnostiknuklid Lu-177 weist dabei neben der Therapie-relevanten Beta-Minus-Komponente eine, auch für die Bildgebung gut nutzbare, Gammaemission auf, die eine direkte quantitative Bildgebung und Dosimetrie der Radiopharmakonverteilung möglich macht. Die Patienten-spezifische 3D-Dosimetrie auf Basis der quantitativen Lu-177-Bildgebung ist dabei der Schlüssel hin zur individualisierten Therapiekontrolle und -planung in der RLT und PRRT, in denen bisher vornehmlich noch standardisierte Aktivitätsmengen verabreicht werden. Jedoch ist die Ermittlung robuster Dosiswerte klinisch aufwändig, sowohl bez. des Messaufwands als auch hinsichtlich der Auswertung der Daten, und die starke Variabilität der Dosiswerte und deren Abhängigkeit von der verwendeten Methodik erschweren die Etablierung Therapie-spezifischer Dosis-Wirkungsbeziehungen. Gerade der Vergleich von Dosimetriedaten zwischen den Kliniken erfordert eine systematische und vereinheitlichte Dosimetrie mit akzeptablem klinischem Aufwand. Die Genauigkeit der Dosimetrie ist derzeit v. a. limitiert durch Effekte der Bildgebung. Zusätzliche Fehler können sich bspw. durch eine ungünstige Wahl der gemessenen Datenpunkte, Bewegungsartefakte, Überlagerungseffekte in der planaren Bildgebung oder durch eine nicht vollständig klinisch durchführbare Definition der Zielregion (z. B. Knochenmark) ergeben. Die 3D-Dosimetrie, unter Berücksichtigung zusätzlicher physikalischer oder biologischer Parameter (z. B. Dosisrate), kann in der Radionuklidtherapie einen wichtigen Beitrag zur Etablierung von Dosis-Wirkungsbeziehungen liefern, allerdings ist die klinisch-physiologische Interpretation der 3D-Dosisverteilungen derzeit noch stark limitiert durch Bildartefakte und Bildrauschen in den zur Dosimetrie eingesetzten SPECT-Bildern.

Abstract

Both, radioligand therapy (RLT) using radiolabelled PSMA-ligands (e. g. Lu-177-PSMA-617) and peptide receptor radionuclide therapy (PRRT) using radio-labelled somatostatin analogs (e. g. Lu-177-DOTATATE), evolved as promising therapy options for metastatic, castration-resistant prostate cancer and metastatic or inoperable neuroendocrine tumours. The theragnostic nuclide Lu-177 exhibits a therapy-relevant beta emission, accompanied by a Gamma emission, which can be directly used for quantitative imaging and dosimetry of the radiopharmaceutical distribution. The patient-specific 3D dosimetry based on quantitative Lu-177 imaging is the key to individualized therapy evaluation and planning for Lu-177-RLT and -PRRT, for which – so far – the clinical routine approach still mainly employs fixed activity schedules. However, reliable clinical dosimetry is demanding concerning both, the clinical workload during acquisition of patient-specific data for dosimetry and the technical, physical and clinical evaluation of the data. Furthermore, the strong inter-patient variability of the dose values and their dependence on the exact techniques used for dose evaluation complicate the finding of therapy-specific dose-effect-relationships. Especially the comparability of dose values between different clinical institutions requires a systematic and unified processing of dosimetry data, yet, at a reasonable clinical workload. The accuracy of current dose estimates is mainly limited due to the quality of the quantitative images. Further inaccuracies might be caused by – for example – an insufficient selection of measurement time points, motion artefacts, superposition artefacts during planar-based dosimetry, and an insufficient definition of the target regions (e. g. in case of bone marrow dosimetry). Three-dimensional dosimetry with consideration of radiobiological parameters (e. g. dose rate) can provide an important contribution to the finding of dose-effect-relationships, however, the clinical and physiological evaluation of currently reconstructed quantitative 3D activity distributions of SPECT images is still limited due to image artefacts and noise.

Schlüsselwörter

Radioligandentherapie - Peptid-Rezeptor-Radionuklidtherapie - Radionuklidtherapie - PSMA - DOTATATE - mCRPC - NET - Prostatakarzinom - neuroendokriner Tumor - Dosimetrie - Lu-177

Keywords

radioligand therapy - peptide receptor radionuclide therapy - radionuclide therapy - PSMA - DOTATATE - mCRPC - NET - prostate cancer - neuroendocrine tumour - dosimetry - Lu-177
 

  • Literatur

  • 1 Strosberg J. et al. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 2017; 376: 125-135
    CrossrefPubMedGoogle Scholar
  • 2 Afshar-Oromieh A. et al. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions. J Nucl Med 2015; 56: 1697-1705
    CrossrefPubMedGoogle Scholar
  • 3 Rahbar K. et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med 2017; 58: 85-90
    CrossrefPubMedGoogle Scholar
  • 4 Cremonesi M. et al. Dosimetry in peptide radionuclide receptor therapy: a review. Journal of nuclear medicine 2006; 47: 1467-1475
    PubMedGoogle Scholar
  • 5 Sandström M. et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. Journal of Nuclear Medicine 2013; 54: 33-41
    CrossrefPubMedGoogle Scholar
  • 6 Delker A. et al. Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. European journal of nuclear medicine and molecular imaging 2016; 43: 42-51
    CrossrefPubMedGoogle Scholar
  • 7 Strigari L. et al. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy. European journal of nuclear medicine and molecular imaging 2014; 41: 1976-1988
    CrossrefPubMedGoogle Scholar
  • 8 Stabin MG. Uncertainties in internal dose calculations for radiopharmaceuticals. Journal of nuclear medicine 2008; 49: 853-860
    CrossrefPubMedGoogle Scholar
  • 9 Stabin MG, Flux G. Internal dosimetry as a tool for radiation protection of the patient in nuclear medicine. Biomedical Imaging and Intervention Journal 2007; 3: e28
    PubMedGoogle Scholar
  • 10 Stabin MG, Brill AB. State of the art in nuclear medicine dose assessment. in Seminars in nuclear medicine. Elsevier; 2008. 38, 303-320
    Google Scholar
  • 11 Ilan E. et al. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE. Journal of Nuclear Medicine 2015; 56: 177-182
    CrossrefPubMedGoogle Scholar
  • 12 Bé M. et al. Table of radionuclides (Vol. 2-A= 151 to 242). Bureau international des poids et mesures: Pavillon de Breteuil, Sèvres; 2004
    PubMedGoogle Scholar
  • 13 https://www.nist.gov/pml/stopping-power-range-tables-electrons-protons-and-helium-ions
    PubMed
  • 14 Siegel JA. et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. The Journal of Nuclear Medicine 1999; 40: 37S
    PubMedGoogle Scholar
  • 15 Dewaraja YK. et al. MIRD pamphlet no. 23: quantitative SPECT for patient-specific 3-dimensional dosimetry in internal radionuclide therapy. Journal of Nuclear Medicine 2012; 53: 1310-1325
    CrossrefPubMedGoogle Scholar
  • 16 Ljungberg M. et al. MIRD pamphlet no. 26: joint EANM/MIRD guidelines for quantitative 177Lu SPECT applied for dosimetry of radiopharmaceutical therapy. Journal of Nuclear Medicine 2016; 57: 151-162
    CrossrefPubMedGoogle Scholar
  • 17 Bolch WE. et al. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry – standardization of nomenclature. Journal of Nuclear Medicine 2009; 50: 477-484
    CrossrefPubMedGoogle Scholar
  • 18 Delker A. et al. The influence of early measurements onto the estimated kidney dose in [177Lu][DOTA0, Tyr3] octreotate peptide receptor radiotherapy of neuroendocrine tumors. Molecular Imaging and Biology 2015; 17: 726-734
    CrossrefPubMedGoogle Scholar
  • 19 Garkavij M. 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: 1084-1092
    CrossrefPubMedGoogle Scholar
  • 20 Frey EC, Humm JL, Ljungberg M. Accuracy and precision of radioactivity quantification in nuclear medicine images. In: Seminars in nuclear medicine. Elsevier: 2012. 42, 208-218
    Google Scholar
  • 21 Anizan N. et al. Factors affecting the repeatability of gamma camera calibration for quantitative imaging applications using a sealed source. Physics in medicine and biology 2015; 60: 1325
    CrossrefPubMedGoogle Scholar
  • 22 Chun SY, Fessler JA, Dewaraja YK. Correction for collimator-detector response in SPECT using point spread function template. IEEE transactions on medical imaging 2013; 32: 295-305
    CrossrefPubMedGoogle Scholar
  • 23 Shcherbinin S, Grimes J, Celler A. Two methods to generate templates for template-based partial volume effect correction: SPECT phantom experiments. Physics in medicine and biology 2013; 58: 1103
    CrossrefPubMedGoogle Scholar
  • 24 Boening G, Pretorius PH, King MA. Study of relative quantification of Tc-99 m with partial volume effect and spillover correction for SPECT oncology imaging. IEEE transactions on nuclear science 2006; 53: 1205-1212
    CrossrefPubMedGoogle Scholar
  • 25 Dewaraja YK, Koral KF, Fessler JA. Regularized reconstruction in quantitative SPECT using CT side information from hybrid imaging. Physics in medicine and biology 2010; 55: 2523
    CrossrefPubMedGoogle Scholar
  • 26 Kangasmaa T, Sohlberg A, Kuikka JT. Reduction of collimator correction artefacts with bayesian reconstruction in spect. International journal of molecular imaging 2011; DOI: 10.1155/2011/630813.
    CrossrefPubMedGoogle Scholar
  • 27 Nuyts J. Unconstrained image reconstruction with resolution modelling does not have a unique solution. EJNMMI physics 2014; 1: 98
    CrossrefPubMedGoogle Scholar
  • 28 Bolch WE. et al. MIRD pamphlet No, 17: The dosimetry of nonuniform activity distributions – radionuclide S values at the voxel level. The Journal of Nuclear Medicine 1999; 40: S11
    PubMedGoogle Scholar
  • 29 Grimes J, Celler A. Comparison of internal dose estimates obtained using organ‐level, voxel S value, and Monte Carlo techniques. Medical physics 2014; 41: 092501-1-092501-11
    PubMedGoogle Scholar
  • 30 Konijnenberg M. et al. Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy. Journal of Nuclear Medicine 2007; 48: 134-142
    PubMedGoogle Scholar
  • 31 Emami B. Tolerance of normal tissue to therapeutic radiation. Reports of radiotherapy and Oncology 2013; 1: 35-48
    PubMedGoogle Scholar
  • 32 Emami B. et al. Tolerance of normal tissue to therapeutic irradiation. International Journal of Radiation Oncology* Biology* Physics 1991; 21: 109-122
    PubMedGoogle Scholar
  • 33 Lanconelli N. et al. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions. Physics in medicine and biology 2012; 57: 517
    CrossrefPubMedGoogle Scholar
  • 34 Chiavassa S. et al. OEDIPE: a personalized dosimetric tool associating voxel-based models with MCNPX. Cancer biotherapy & radiopharmaceuticals 2005; 20: 325-332
    CrossrefPubMedGoogle Scholar
  • 35 Botta F. et al. Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images. Physics in medicine and biology 2013; 58: 8099
    CrossrefPubMedGoogle Scholar
  • 36 Wilderman S, Dewaraja Y. Method for fast CT/SPECT-based 3D Monte Carlo absorbed dose computations in internal emitter therapy. IEEE transactions on nuclear science 2007; 54: 146-151
    CrossrefPubMedGoogle Scholar
  • 37 Lehmann J. et al. Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system. Physics in medicine and biology 2005; 50: 947
    CrossrefPubMedGoogle Scholar
  • 38 Yoriyaz H, Stabin MG, dos Santos A. Monte Carlo MCNP-4B-based absorbed dose distribution estimates for patient-specific dosimetry. Journal of Nuclear Medicine 2001; 42: 662-669
    PubMedGoogle Scholar
  • 39 Ljungberg M. et al. 3D absorbed dose calculations based on SPECT: evaluation for 111-In/90-Y therapy using Monte Carlo simulations. Cancer Biotherapy and Radiopharmaceuticals 2003; 18: 99-107
    CrossrefPubMedGoogle Scholar
  • 40 Ljungberg M, Sjögreen-Gleisner K. The accuracy of absorbed dose estimates in tumours determined by quantitative SPECT: a Monte Carlo study. Acta Oncologica 2011; 50: 981-989
    CrossrefPubMedGoogle Scholar
  • 41 He B, Frey EC. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods. Physics in medicine and biology 2010; 55: 3535
    CrossrefPubMedGoogle Scholar
  • 42 Forrer F. et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0, Tyr3] octreotate. European journal of nuclear medicine and molecular imaging 2009; 36: 1138
    CrossrefPubMedGoogle Scholar
  • 43 Hindorf C. et al. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. European journal of nuclear medicine and molecular imaging 2010; 37: 1238-1250
    CrossrefPubMedGoogle Scholar
  • 44 Sgouros G. et al. Red marrow dosimetry for radiolabeled antibodies that bind to marrow, bone, or blood components. Medical physics 2000; 27: 2150-2164
    CrossrefPubMedGoogle Scholar
  • 45 Traino A. et al. Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry. Physics in medicine and biology 2007; 52: 5231
    CrossrefPubMedGoogle Scholar
  • 46 Gosewisch A. et al. Estimation of local photon dose to active bone marrowin Lu-177 PSMA PRRT therapy using patient-specific Monte Carlo simulations. European Journal of Nuclear Medicine and Molecular Imaging 2015; 42: S754-S755
    PubMedGoogle Scholar
  • 47 Gustafsson J. et al. Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy. Physics in medicine and biology 2015; 60: 8329
    CrossrefPubMedGoogle Scholar
  • 48 Dale R. Dose-rate effects in targeted radiotherapy. Physics in medicine and biology 1996; 41: 1871
    CrossrefPubMedGoogle Scholar
  • 49 Baum RP. et al. Lutetium-177 PSMA radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. Journal of Nuclear Medicine 2016; DOI: p.jnumed.115.168443.
    CrossrefPubMedGoogle Scholar
  • 50 Kabasakal L. et al. Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Bio-distribution and Dosimetry. Molecular imaging and radionuclide therapy 2017; 26: 62
    CrossrefPubMedGoogle Scholar
  • 51 Gupta SK. et al. Dosimetric analyses of kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors of patients treated with 177Lu-DOTATATE. Clinical nuclear medicine 2013; 38: 188-194
    CrossrefPubMedGoogle Scholar
  • 52 Larsson M. et al. Estimation of absorbed dose to the kidneys in patients after treatment with 177 Lu-octreotate: comparison between methods based on planar scintigraphy. EJNMMI research 2012; 2: 49
    CrossrefPubMedGoogle Scholar