Der Nuklearmediziner 2021; 44(04): 355-368
DOI: 10.1055/a-1556-8361
Quo vadis NET?

Bild-basierte Patienten-individuelle Dosimetrie bei internen Radionuklidtherapien von neuroendokrinen Tumoren

Image-based patient-specific dosimetry for internal radionuclide therapies of neuroendocrine tumors
Julia Brosch-Lenz*
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, Deutschland
,
Astrid Gosewisch*
Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, Deutschland
› Author Affiliations

Zusammenfassung

Die Peptid-Radiorezeptor-Therapie (PRRT) mit Lutetium-177 (177Lu) hat sich als vielversprechende Therapieoption von metastasierten neuroendokrinen Tumoren (NETs) etabliert. Des Weiteren wird die Yttrium-90 (90Y) selektive interne Radio-Therapie (SIRT) als lokale Therapie von Lebermetastasen von NET Patienten durchgeführt. Beide Therapien werden von quantitativer Bildgebung begleitet und ermöglichen so Therapie-begleitende, Patienten-individuelle Dosimetrie. Die Abschätzung der Strahlendosis auf Risikoorgane und Tumore hat den großen Vorteil, dass weitere geplante Therapiezyklen möglicherweise angepasst werden können, um sowohl den Therapieerfolg zu verbessern, als auch die Nebenwirkung durch Toxizität von Risikoorganen zu minimieren. Die PRRT und SIRT unterscheiden sich sowohl in der Applikation, dem zugrundeliegenden therapeutischen Konzept, als auch den Radionukliden. Daraus resultieren verschiedene Anforderungen und Voraussetzungen für die Dosimetrie. Dieser Artikel beleuchtet detailliert die verschiedenen Herausforderungen für Bild-basierte Dosimetrie bei der PRRT und der SIRT von NET Patienten und unterstreicht die Notwendigkeit von routinemäßiger Dosimetrie.

Abstract

Peptide Receptor Radionuclide Therapy (PRRT) using Lutetium-177 (177Lu) has become a promising therapeutic option for metastasized neuroendocrine tumors (NETs). In addition, selective internal radionuclide therapy (SIRT) using Yttrium-90 (90Y) can serve as local therapy option for liver metastases of NET patients. Both therapies are accompanied by quantitative imaging which allows for pre- and post-therapeutic, patient-specific dosimetry. The estimation of absorbed radiation dose to organs at risk and tumors offers the potential that subsequent therapy cycles could be adapted to maximize therapy success while minimizing the risk of therapy related side effects or organ toxicities. PRRT and SIRT differ in application, underlying therapeutic concepts, and radionuclides, which leads to different demands and requirements for image-based dosimetry. This article reviews in detail the different challenges for image-based dosimetry for both, PRRT and SIRT, for NET patients. We further would like to underline the need for routine dosimetry.

* Beide Autorinnen haben zu gleichen Teilen zu diesem Manuskript beigetragen.




Publication History

Article published online:
29 November 2021

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  • Literatur

  • 1 Dasari A, Shen C, Halperin D. et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA oncology 2017; 3: 1335-42
  • 2 Riihimäki M, Hemminki A, Sundquist K. et al. The epidemiology of metastases in neuroendocrine tumors. International journal of cancer 2016; 139: 2679-86
  • 3 Pavel M, Costa F, Capdevila J. et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 2016; 103: 172-85
  • 4 Reubi JC. Somatostatin and other peptide receptors as tools for tumor diagnosis and treatment. Neuroendocrinology 2004; 80 (Suppl. 01) 51-56
  • 5 Yordanova A, Eppard E, Kürpig S. et al. Theranostics in nuclear medicine practice. OncoTargets and therapy 2017; 10: 4821
  • 6 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. New England Journal of Medicine 2017; 376: 125-35
  • 7 Zaknun JJ, Bodei L, Mueller-Brand J. et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. European journal of nuclear medicine and molecular imaging 2013; 40: 800-816
  • 8 Jia Z, Wang W. Yttrium-90 radioembolization for unresectable metastatic neuroendocrine liver tumor: A systematic review. European journal of radiology 2018; 100: 23-29
  • 9 Union CotE. Council Directive 2013/59/Euratom of 5 December 2013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives 89/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom. Off J Eur Commun 2014; 13: 1-73
  • 10 Selwyn RG, Nickles RJ, Thomadsen BR. et al. A new internal pair production branching ratio of 90Y: the development of a non-destructive assay for 90Y and 90Sr. Appl Radiat Isot 2007; 65 (03) 318-27
  • 11 Seltzer S, Bartlett D, Burns D. et al. ICRU report 85 fundamental quantities and units for ionizing radiation. J ICRU; 2011 11
  • 12 Dewaraja YK, Frey EC, Sgouros G. 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
  • 13 Gosewisch A, Ilhan H, Vomacka L. et al. Dosimetrie bei der Radionuklidtherapie mit Lu-177. Der Nuklearmediziner 2018; 41 (01) 69-80
  • 14 Snyder W, Ford M, Warner G, Watson S. MIRD pamphlet no. 11. New York: The Society of Nuclear Medicine; 1975: 92-93
  • 15 Bolch WE, Bouchet LG, Robertson JS. et al. MIRD pamphlet no. 17: the dosimetry of nonuniform activity distributions—radionuclide S values at the voxel level. Journal of Nuclear Medicine 1999; 40: 11S-36S
  • 16 Stabin MG, Siegel JA. RADAR dose estimate report: a compendium of radiopharmaceutical dose estimates based on OLINDA/EXM version 2.0. Journal of Nuclear Medicine 2018; 59: 154-160
  • 17 Bé M-M, Chisté V, Dulieu C. et al. Table of radionuclides (Vol. 2-A= 151 to 242). Monographie BIPM-5; 2004 2. 1-307
  • 18 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. Journal of nuclear medicine 2016; 57: 151-162
  • 19 Werner RA, Weich A, Kircher M. et al. The theranostic promise for Neuroendocrine Tumors in the late 2010s-Where do we stand, where do we go?. Theranostics 2018; 8: 6088
  • 20 Ilhan H, Lindner S, Todica A. et al. Biodistribution and first clinical results of 18 F-SiFA lin-TATE PET: a novel 18 F-labeled somatostatin analog for imaging of neuroendocrine tumors. European journal of nuclear medicine and molecular imaging 2019; 47: 870-880
  • 21 Baum RP, Kulkarni HR. THERANOSTICS: from molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy-the Bad Berka experience. Theranostics 2012; 2: 437
  • 22 Werner P, Neumann C, Eiber M. et al. [99cm Tc] Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. EJNMMI research 2020; 10: 1-10
  • 23 Reubi J, Waser B, Schaer J-C. et al. Somatostatin receptor sst1–sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. European journal of nuclear medicine 2001; 28: 836-46
  • 24 Garske-Román U, Sandström M, Baron KF. et al. Prospective observational study of 177 Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. European journal of nuclear medicine and molecular imaging 2018; 45: 970-88
  • 25 Sandström M, Garske-Román U, Granberg D. et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. Journal of Nuclear Medicine 2013; 54: 33-41
  • 26 Sandström M, Garske U, Granberg D. et al. Individualized dosimetry in patients undergoing therapy with 177 Lu-DOTA-D-Phe 1-Tyr 3-octreotate. European journal of nuclear medicine and molecular imaging 2010; 37: 212-25
  • 27 Sundlöv A, Sjögreen-Gleisner K, Svensson J. et al. Individualised 177 Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry. European journal of nuclear medicine and molecular imaging 2017; 44: 1480-1489
  • 28 Sabet A, Haslerud T, Pape U-F. et al. Outcome and toxicity of salvage therapy with 177 Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours. European journal of nuclear medicine and molecular imaging 2014; 41: 205-210
  • 29 Van der Zwan W, Brabander T, Kam B. et al. Salvage peptide receptor radionuclide therapy with [177 Lu-DOTA, Tyr 3] octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. European journal of nuclear medicine and molecular imaging 2019; 46: 704-717
  • 30 Rudisile S, Gosewisch A, Wenter V. et al. Salvage PRRT with 177 Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival. BMC cancer 2019; 19: 1-9
  • 31 Svensson J, Berg G, Wängberg B. et al. Renal function affects absorbed dose to the kidneys and haematological toxicity during 177 Lu-DOTATATE treatment. European journal of nuclear medicine and molecular imaging 2015; 42: 947-955
  • 32 Bolch WE, Eckerman KF, Sgouros G. et al. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry—standardization of nomenclature. Journal of Nuclear Medicine 2009; 50: 477-484
  • 33 Dale R. Dose-rate effects in targeted radiotherapy. Physics in Medicine & Biology 1996; 41: 1871
  • 34 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. Journal of Nuclear Medicine 2008; 49: 1884-1899
  • 35 Ballal S, Yadav MP, Bal C. et al. Broadening horizons with 225 Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177 Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. European journal of nuclear medicine and molecular imaging 2019; 47: 934-946
  • 36 Barone R, Borson-Chazot F, Valkema R. et al. Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose–effect relationship. Journal of nuclear medicine 2005; 46 (Suppl. 01) 99S-106S
  • 37 Konijnenberg M, Melis M, Valkema R. et al. Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy. Journal of Nuclear Medicine 2007; 48: 134-42
  • 38 Hagmarker L, Svensson J, Rydén T. et al. Bone marrow absorbed doses and correlations with hematologic response during 177Lu-DOTATATE treatments are influenced by image-based dosimetry method and presence of skeletal metastases. Journal of Nuclear Medicine 2019; 60: 1406-1413
  • 39 Garkavij M, Nickel M, Sjögreen-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 (Suppl. 04) 1084-1092
  • 40 Huizing DMV, Verheij M, Stokkel MPM. Dosimetry methods and clinical applications in peptide receptor radionuclide therapy for neuroendocrine tumours: a literature review. EJNMMI research 2018; 8: 1-11
  • 41 Delker A, Ilhan H, Zach C. et al. The influence of early measurements onto the estimated kidney dose in [177 Lu][DOTA 0, Tyr 3] Octreotate peptide receptor radiotherapy of neuroendocrine tumors. Molecular imaging and biology 2015; 17: 726-734
  • 42 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. Journal of Nuclear Medicine 1999; 40: 37S-61S
  • 43 Rinscheid A, Kletting P, Eiber M. et al. Influence of sampling schedules on [177 Lu] Lu-PSMA dosimetry. EJNMMI physics 2020; 7: 1-14
  • 44 Hänscheid H, Lapa C, Buck AK. et al. Dose mapping after endoradiotherapy with 177Lu-DOTATATE/DOTATOC by a single measurement after 4 days. Journal of Nuclear Medicine 2018; 59: 75-81
  • 45 Sundlöv A, Gustafsson J, Brolin G. et al. Feasibility of simplifying renal dosimetry in 177 Lu peptide receptor radionuclide therapy. EJNMMI physics 2018; 5: 1-19
  • 46 Willowson KP, Eslick E, Ryu H. et al. Feasibility and accuracy of single time point imaging for renal dosimetry following 177 Lu-DOTATATE (‘Lutate’) therapy. EJNMMI physics 2018; 5: 1-9
  • 47 Zhao W, Esquinas PL, Frezza A. et al. Accuracy of kidney dosimetry performed using simplified time activity curve modelling methods: a 177Lu-DOTATATE patient study. Physics in Medicine & Biology 2019; 64: 175006
  • 48 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. Journal of Nuclear Medicine 2003; 44: 1113-47
  • 49 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
  • 50 Chiesa C, Bardiès M, Zaidi H. Voxel-based dosimetry is superior to mean-absorbed dose approach for establishing dose-effect relationship in targeted radionuclide therapy. Medical physics 2019; 46: 5403-5406
  • 51 Hindorf C, Glatting G, Chiesa 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
  • 52 Forrer F, Krenning EP, Kooij PP. et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177 Lu-DOTA 0, Tyr 3] octreotate. European journal of nuclear medicine and molecular imaging 2009; 36: 1138-1146
  • 53 Svensson J, Rydén T, Hagmarker L. et al. A novel planar image-based method for bone marrow dosimetry in 177 Lu-DOTATATE treatment correlates with haematological toxicity. EJNMMI physics 2016; 3: 1-12
  • 54 Gustafsson J, Brolin G, Cox M. et al. Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy. Physics in Medicine & Biology 2015; 60: 8329
  • 55 Finocchiaro D, Gear JI, Fioroni F. et al. Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy. EJNMMI physics 2020; 7: 1-16
  • 56 Gosewisch A, Delker A, Tattenberg S. et al. Patient-specific image-based bone marrow dosimetry in Lu-177-[DOTA 0, Tyr 3]-Octreotate and Lu-177-DKFZ-PSMA-617 therapy: investigation of a new hybrid image approach. EJNMMI research 2018; 8: 1-16
  • 57 Saini A, Wallace A, Alzubaidi S. et al. History and evolution of yttrium-90 radioembolization for hepatocellular carcinoma. Journal of clinical medicine 2019; 8: 55
  • 58 Gulec SA, Mesoloras G, Dezarn WA. et al. Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: the tumor selectivity of the treatment as a function of tumor to liver flow ratio. Journal of translational medicine 2007; 5: 1-9
  • 59 D'Avola D, Lñarrairaegui M, Bilbao JI. et al. A retrospective comparative analysis of the effect of Y90-radioembolization on the survival of patients with unresectable hepatocellular carcinoma. Hepato-gastroenterology 2009; 56: 1683-8
  • 60 Raval M, Bande D, Pillai AK. et al. Yttrium-90 radioembolization of hepatic metastases from colorectal cancer. Frontiers in oncology 2014; 4: 120
  • 61 Fendler WP, Lechner H, Todica A. et al. Safety, efficacy, and prognostic factors after radioembolization of hepatic metastases from breast cancer: a large single-center experience in 81 patients. Journal of Nuclear Medicine 2016; 57: 517-23
  • 62 Hilgard P, Hamami M, Fouly AE. et al. Radioembolization with yttrium‐90 glass microspheres in hepatocellular carcinoma: European experience on safety and long‐term survival. Hepatology 2010; 52: 1741-9
  • 63 Kennedy AS, Ball D, Cohen SJ. et al. Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for 90Y resin microspheres. Journal of gastrointestinal oncology 2015; 6 (02) 134
  • 64 Mouli S, Memon K, Baker T. et al. Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. Journal of Vascular and Interventional Radiology 2013; 24: 1227-34
  • 65 Devcic Z, Rosenberg J, Braat AJ. et al. The efficacy of hepatic 90Y resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis. Journal of Nuclear Medicine 2014; 55: 1404-10
  • 66 Hellwig D, Marienhagen J, Menhart K. et al. Nuklearmedizin in Deutschland. Nuklearmedizin 2017; 56: 55-68
  • 67 Kennedy A, Nag S, Salem R. et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 2007; 68: 13-23
  • 68 Cremonesi M, Ferrari M, Bodei L. et al. Dosimetry in peptide radionuclide receptor therapy: a review. Journal of nuclear medicine 2006; 47: 1467-1475
  • 69 Ilhan H, Goritschan A, Paprottka P. et al. Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization. J Nucl Med 2015; 56: 333-338
  • 70 Levillain H, Bagni O, Deroose CM. et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. European journal of nuclear medicine and molecular imaging 2021; 48: 1570-1584
  • 71 Ho S, Lau WY, Leung TW. et al. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours. Eur J Nucl Med 1996; 23: 947-952
  • 72 Chansanti O, Jahangiri Y, Matsui Y. et al. Tumor dose response in Yttrium-90 resin microsphere embolization for neuroendocrine liver metastases: a tumor-specific analysis with dose estimation using SPECT-CT. Journal of Vascular and Interventional Radiology 2017; 28: 1528-1535
  • 73 Dezarn WA, Cessna JT, DeWerd LA. et al. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies. Medical Physics 2011; 38: 4824-4845
  • 74 Lhommel R, van Elmbt L, Goffette P. et al. Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres. Eur J Nucl Med Mol Imaging 2010; 37: 1654-1662
  • 75 Willowson KP, Tapner M, Team QI. 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: 1202-1222
  • 76 Rong X, Du Y, Frey EC. A method for energy window optimization for quantitative tasks that includes the effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT imaging. Phys Med Biol 2012; 57: 3711-3725
  • 77 Rong X, Du Y, Ljungberg M. et al. Development and evaluation of an improved quantitative (90)Y bremsstrahlung SPECT method. Med Phys 2012; 39: 2346-2358
  • 78 Rong X, Frey EC. A collimator optimization method for quantitative imaging: application to Y-90 bremsstrahlung SPECT. Med Phys 2013; 40: 082504
  • 79 Siman W, Mikell J, Kappadath S. Practical reconstruction protocol for quantitative 90Y bremsstrahlung SPECT/CT. Medical physics 2016; 43: 5093-5103
  • 80 Dewaraja YK, Chun SY, Srinivasa RN. et al. Improved quantitative 90Y bremsstrahlung SPECT/CT reconstruction with Monte Carlo scatter modeling. Medical physics 2017; 44: 6364-6376
  • 81 Yue J, Mauxion T, Reyes DK. et al. Comparison of quantitative Y-90 SPECT and non-time-of-flight PET imaging in post-therapy radioembolization of liver cancer. Med Phys 2016; 43: 5779
  • 82 Elschot M, Vermolen BJ, Lam MG. et al. Quantitative comparison of PET and Bremsstrahlung SPECT for imaging the in vivo yttrium-90 microsphere distribution after liver radioembolization. PLoS One 2013; 8: e55742
  • 83 Brosch J, Gosewisch A, Kaiser L. et al. 3D image-based dosimetry for Yttrium-90 radioembolization of hepatocellular carcinoma: Impact of imaging method on absorbed dose estimates. Physica Medica 2020; 80: 317-26
  • 84 Mikell JK, Mahvash A, Siman W. et al. Comparing voxel-based absorbed dosimetry methods in tumors, liver, lung, and at the liver-lung interface for (90)Y microsphere selective internal radiation therapy. EJNMMI Phys 2015; 2: 16
  • 85 Braat A, Kappadath S, Ahmadzadehfar H. et al. Radioembolization with 90 Y resin microspheres of neuroendocrine liver metastases: international multicenter study on efficacy and toxicity. Cardiovascular and interventional radiology 2019; 42: 413-425