[en] The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Herrmann, Ken; Department of Nuclear Medicine, University of Duisburg-Essen, Duisburg, Germany, ken2404@web.de ; German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
Giovanella, Luca; Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Santos, Andrea; Department of Nuclear Medicine, Hospital Cuf Descobertas, Lisbon, Portugal
Gear, Jonathan; Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton, Sutton, United Kingdom
Ozgen Kiratli, Pinar; Department of Nuclear Medicine, Hacettepe University, Ankara, Turkey
Kurth, Jens; Department of Nuclear Medicine, Rostock University Medical Center, Rostock, Germany
Denis-Bacelar, Ana M; National Physical Laboratory, Teddington, United Kingdom
Hustinx, Roland ; Centre Hospitalier Universitaire de Liège - CHU > > Service médical de médecine nucléaire et imagerie onco
Patt, Marianne; Department for Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany
Wahl, Richard L; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
Paez, Diana; Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Application, International Atomic Energy Agency, Vienna, Austria
Giammarile, Francesco; Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Application, International Atomic Energy Agency, Vienna, Austria
Jadvar, Hossein; Division of Nuclear Medicine, Department of Radiology, University of Southern California, Los Angeles, California
Pandit-Taskar, Neeta; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
Ghesani, Munir; Diagnostic, Molecular & Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, and
Kunikowska, Jolanta; Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland
Conflicts of interest: KH reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novar-tis, personal fees from ymabs, all outside the submitted work. LG reports personal fees from Roche Diagnostics and SNIBE for advisory board participation, and research support from Roche Diagnostics., all outside the submitted work. AMDB is supported by the National Measurement System of the UK Department for Business, Energy and Industrial Strategy. RLW has research contracts from Siemens, Bayer, Actinium Pharmaceuticals, and serves (with compensation) on the scientific advisory boards of Seno Medical and Clarity Pharmaceuticals. HJ serves on the advisory board of Radiomedix, is a consultant to Bayer and Blue Earth Diagnostics, an investigator for ImaginAb, and on the speaker’s bureau of Lantheus. MG reports fee for speakers bureau of Novar-tis, Blue Earth and Ionetix (not active currently). The remaining authors have no relevant conflict of interest to declare with regards to this comment.This guideline was only possible thanks to the tremendous support of the EANM headquarters and especially Nuria Serra. The authors want to eternally thank them for their support, help and patience.
Kaminski MS, Zasadny KR, Francis IR, et al. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993;329:459–465.
Morschhauser F, Radford J, Van Hoof A, et al. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial. J Clin Oncol. 2013;31: 1977–1983.
Zippel C, Giesel FL, Kratochwil C, et al. PSMA radioligand therapy could pose infrastructural challenges for nuclear medicine: results of a basic calculation for the capacity planning of nuclear medicine beds in the German hospital sector. Nucl Med (Stuttg). 2021;60:216–223.
Czernin J, Sonni I, Razmaria A, Calais J. The future of nuclear medicine as an independent specialty. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2019;60(suppl 2):3S–12S.
Radiation Protection and Safety of Radiation Sources: International Basic Safety Standards. Vienna: INTERNATIONAL ATOMIC ENERGY AGENCY; 2014.
The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37:1–332.
ICRP Publication 105. Radiation protection in medicine. Ann ICRP. 2007;37: 1–63.
Thisgaard H, Kumlin J, Langkjaer N, et al. Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE. EJNMMI Radiopharm Chem. 2021;6:1.
Radchenko V, Morgenstern A, Jalilian AR, et al. Production and Supply of alpha-Particle-Emitting Radionuclides for Targeted alpha-Therapy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2021; 62(11):1495–1503.
Gadd R, Baker M, Nijran KS, et al. Protocol for Establishing and Maintaining the Calibration of Medical Radionuclide Calibrators and their Quality Control, 2006.
AAPM. The selection, use, calibration and quality assurance of radionuclide calibrators used in nuclear medicine: American Association of Physicist in Medicine, 2012.
IAEA. Quality assurance for radioactivity measurement in nuclear medicine. Vienna: Internation Atomic Energy Agency, 2006.
EANM PC, Busemann Sokole E, Plachcinska A, et al. Routine quality control recommendations for nuclear medicine instrumentation. Eur J Nucl Med Mol Imaging. 2010;37:662–671.
Busemann Sokole E, Plachcinska A, Britten A, Committee EP. Acceptance testing for nuclear medicine instrumentation. Eur J Nucl Med Mol Imaging. 2010; 37:672–681.
ICRP. Release of patients after therapy with unsealed radionuclides. Ann ICRP. 2004;34:v–vi, 1–79.
Erratum to “ICRP Publication 94: Release of patients after therapy with unsealed radionuclides.” Ann ICRP [Ann ICRP 34(2)]. 2004;34:281.
IAEA. Release of Patients After Radionuclide Therapy. Vienna: International Atomic Energy Agency; 2009.
Demir M, Abuqbeitah M, Uslu-Besli L, et al. Evaluation of radiation safety in (177)Lu-PSMA therapy and development of outpatient treatment protocol. J Radiol Prot. 2016;36:269–278.
Kurth J, Krause BJ, Schwarzenbock SM, Stegger L, Schafers M, Rahbar K. External radiation exposure, excretion, and effective half-life in (177)Lu-PSMA-targeted therapies. EJNMMI Res. 2018;8:32.
Levart D, Kalogianni E, Corcoran B, Mulholland N, Vivian G. Radiation precautions for inpatient and outpatient (177)Lu-DOTATATE peptide receptor radionuclide therapy of neuroendocrine tumours. EJNMMI Phys. 2019;6:7.
Konijnenberg M, Herrmann K, Kobe C, et al. EANM position paper on article 56 of the Council Directive 2013/59/Euratom (basic safety standards) for nuclear medicine therapy. Eur J Nucl Med Mol Imaging. 2021;48:67–72.
Hricak H, Abdel-Wahab M, Atun R, et al. Medical imaging and nuclear medicine: a Lancet Oncology Commission. Lancet Oncol. 2021;22:e136–e72.
Craig AJ, Rojas B, Wevrett JL, Hamer E, Fenwick A, Gregory R. IPEM topical report: current molecular radiotherapy service provision and guidance on the implications of setting up a dosimetry service. Phys Med Biol. 2020;65:245038.
Mora-Ramirez E, Santoro L, Cassol E, et al. Comparison of commercial dosimetric software platforms in patients treated with (177) Lu-DOTATATE for peptide receptor radionuclide therapy. Med Phys. 2020;47:4602–4615.
Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry—Standardization of Nomenclature. J Nucl Med. 2009;50:477–484.
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: official publication, Society of Nuclear Medicine. 2012;53(8):1310–1325.
Hindorf C, Glatting G, Chiesa C, Linden O, Flux G, Committee ED. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging. 2010;37:1238–1250.
EARL. 2022. https://earl.eanm.org/. Accessed 28 Feb 2022.
Committee ET. Technologistś Guide. 2022. https://www.eanm.org/publications/technologists-guide/. Accessed 28 Feb 2022.
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;57:151–162.
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;40:800–816.
Lassmann M, Chiesa C, Flux G, Bardies M, Committee ED. EANM Dosimetry Committee guidance document: good practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging. 2011;38:192–200.
Gear JI, Cox MG, Gustafsson J, et al. EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations. Eur J Nucl Med Mol Imaging. 2018;45:2456–2474.
Dewaraja YK, Ljungberg M, Green AJ, et al. MIRD pamphlet No. 24: Guidelines for quantitative 131I SPECT in dosimetry applications. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2013;54(12): 2182–2188.
Taprogge J, Leek F, Schurrat T, et al. Setting up a quantitative SPECT imaging network for a European multi-centre dosimetry study of radioiodine treatment for thyroid cancer as part of the MEDIRAD project. EJNMMI Phys. 2020;7:61.
Hanscheid H, Canzi C, Eschner W, et al. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases. Eur J Nucl Med Mol Imaging. 2013;40:1126–1134.
Lassmann M, Hanscheid H, Chiesa C, et al. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging. 2008;35:1405–1412.
Gear J, Chiesa C, Lassmann M, et al. EANM Dosimetry Committee series on standard operational procedures for internal dosimetry for (131)I mIBG treatment of neuroendocrine tumours. EJNMMI Phys. 2020;7:15.
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: official publication, Society of Nuclear Medicine. 2016;57(1):151–162.
Tran-Gia J, Denis-Bacelar AM, Ferreira KM, et al. A multicentre and multinational evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project. EJNMMI Phys. 2021;8:55.
Peters SMB, van der Werf NR, Segbers M, et al. Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study. EJNMMI Phys. 2019;6:29.
Chiesa C, Sjogreen-Gleisner K, Walrand S, et al. EANM dosimetry committee series on standard operational procedures: a unified methodology for (99m)Tc-MAA pre- and (90)Y peri-therapy dosimetry in liver radioembolization with (90)Y microspheres. EJNMMI Phys. 2021;8:77.
Hindorf C, Chittenden S, Aksnes AK, Parker C, Flux GD. Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl Med Commun. 2012;33:726–732.
Murray I, Chittenden SJ, Denis-Bacelar AM, et al. The potential of (223)Ra and (18)F-fluoride imaging to predict bone lesion response to treatment with (223)Ra-dichloride in castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1832–1844.
Chittenden SJ, Hindorf C, Parker CC, et al. A Phase 1, Open-Label Study of the Bio-distribution, Pharmacokinetics, and Dosimetry of 223Ra-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2015;56(9):1304–1309.
SNMMI. Procedure Standards. https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=64142021). Accessed 28 Feb 2022.
Fendler WP, Eiber M, Beheshti M, et al. (68)Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–1024.
Kratochwil C, Fendler WP, Eiber M, et al. EANM procedure guidelines for radionuclide therapy with (177)Lu-labelled PSMA-ligands ((177)Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2019;46:2536–2544.
Poeppel TD, Handkiewicz-Junak D, Andreeff M, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:824–845.
EANM. Guidelines. https://www.eanm.org/publications/guidelines/2021). Accessed 28 Feb 2022.
