Eur J Nucl Med Mol Imaging (2008) 35:1039–1047 DOI 10.1007/s00259-008-0715-3 GUIDELINES EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy Francesco Giammarile & Arturo Chiti & Michael Lassmann & Boudewijn Brans & Glenn Flux Published online: 15 February 2008 # EANM 2008 Abstract Meta-iodobenzylguanidine, or Iobenguane, is an nervous system. The neuroendocrine system is derived from a aralkylguanidine resulting from the combination of the family of cells originating in the neural crest, characterized by benzyl group of bretylium and the guanidine group of an ability to incorporate amine precursors with subsequent guanethidine (an adrenergic neurone blocker). It is a decarboxylation. The purpose of this guideline is to assist noradrenaline (norepinephrine) analogue and so-called nuclear medicine practitioners to evaluate patients who might “false” neurotransmitter. This radiopharmaceutical, labeled be candidates for 131I-meta-iodobenzylguanidine to treat with 131I, could be used as a radiotherapeutic metabolic agent neuro-ectodermal tumours, to provide information for in neuroectodermal tumours, that are derived from the performing this treatment and to understand and evaluate primitive neural crest which develops to form the sympathetic the consequences of therapy. F. Giammarile (*) Keywords Guidelines . Therapy . mIBG CH Lyon Sud, EA 3738, HCL, UCBL, 165 Chemin du Grand Revoyet, Purpose 69495 Pierre Benite Cedex, France e-mail: [email protected] The purpose of this guideline is to assist nuclear medicine A. Chiti practitioners to U.O. di Medicina Nucleare, Istituto Clinico Humanitas, via Manzoni, 56, 1. Evaluate patients who might be candidates for 131I-meta- 20089 Rozzano (MI), Italy iodobenzylguanidine (mIBG) to treat neuro-ectodermal e-mail: [email protected] tumours M. Lassmann 2. Provide information for performing this treatment Klinik und Poliklinik für Nuklearmedizin, 3. Understand and evaluate the consequences of therapy Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany e-mail: [email protected] Background information and definitions B. Brans Definitions Department of Nuclear Medicine, University Medical Center Maastricht, P. Debyelaan 25, Postbox 5800, The following are the definitions in this guideline: 6202 AZ Maastricht, 131 The Netherlands 1. I is a beta-emitting radionuclide with a physical half- e-mail: [email protected] life of 8.04 days, a principal gamma ray of 364 KeV (81% abundance) and beta particles with a maximum energy of G. Flux 0.61 MeV and an average energy of 0.192 Mev. Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK 2. mIBG or Iobenguane is an aralkylguanidine resulting e-mail: [email protected] from the combination of the benzyl group of bretylium 1040 Eur J Nucl Med Mol Imaging (2008) 35:1039–1047 and the guanidine group of guanethidine (an adrenergic Contra-indications neurone blocker). It is a noradrenaline (norepinephrine) analogue and a so-called false neurotransmitter. Absolute 3. The neuroendocrine system is derived from a family of cells originating in the neural crest and is characterised The following are absolute contra-indications: by an ability to incorporate amine precursors with 1. Pregnancy; breastfeeding subsequent decarboxylation. 2. Life expectancy less than 3 months, unless in case of 4. Neuroectodermal tumours derive from the primitive intractable bone pain neural crest, which develops to form the sympathetic 3. Renal insufficiency, requiring dialysis on short term nervous system. 5. Therapy in this context means the intravenous infusion of 131I-mIBG. Relative 6. Malignant neuroectodermal tumours in this context include phaeochromocytoma, paraganglioma, carcinoid The following are relative contra-indications: tumours, medullary thyroid cancer and neuroblastoma. 1. Unacceptable medical risk for isolation 2. Unmanageable urinary incontinence Background 3. Rapidly deteriorating renal function—glomerular filtra- tion rate less than 30 ml/min Because of the structural similarity with noradrenaline, after 4. Progressive haematological and/or renal toxicity be- intravenous injection, 131I-mIBG is selectively concentrat- cause of prior treatment ed by tissues with rich adrenergic innervation, essentially 5. Myelosuppression: neuroectodermal tissue, including tumours of neuroecto- – Total white cell count less than 3.0×109/l dermal origin. mIBG may be taken into cells by either the – Platelets less than 100×109/l neuronal uptake-1 mechanism or by passive diffusion and stored in neurosecretory granules (in neuroblastoma, neu- In case of low white blood cell counts, low platelet rosecretory granules are thought to play a minor role and a counts, massive bone marrow invasion and/or impaired fast re-uptake after passive outward diffusion is suggested). renal function, the administered activity should be reduced, The transfer of mIBG from intracellular cytoplasm into and close follow-up is recommended to anticipate toxicity. catecholamine storage vesicles (neurosecretory vesicles) is mediated by an ATPase-dependent proton pump. Unlike noradrenaline, mIBG is not metabolised and is excreted Procedure unchanged [1]. The presumed mechanism of action is the emission of Facility and personnel ionising radiation from the decaying radionuclide 131I. Ninety percent of the radiation effects result from the beta The facilities requirements will depend on national legisla- radiation, which has a mean range in tissue of about tion on the therapeutic use of radioactive-emitting agents. 0.5 mm [2–6]. Most of the time, in-patient treatment is required by national legislation; therefore, this should take place in an approved facility with appropriately shielded rooms and en- suite bathroom facilities. Indications The facility in which treatment is administered must have appropriate personnel, radiation safety equipment, The indications are tumours showing adequate uptake and procedures available for waste handling and disposal, retention of radiolabelled mIBG on the basis of a pre- handling of contamination, monitoring personnel for acci- therapy tracer study. Because there is no clear agreement on dental contamination and controlling contamination spread. what should be considered adequate uptake, the final decision The administration of 131I should be undertaken by must be based on imaging and clinical considerations: appropriately trained medical staff with supporting nursing 1. Inoperable phaeochromocytoma staff and available medical physics expert (according to 2. Inoperable paraganglioma European directive EURATOM 97/43) [7]. 3. Inoperable carcinoid tumour Physicians responsible for treating patients should have 4. Stage III or IV neuroblastoma an understanding of the clinical pathophysiology and natural 5. Metastatic or recurrent medullary thyroid cancer history of the disease processes, should be familiar with Eur J Nucl Med Mol Imaging (2008) 35:1039–1047 1041 other forms of therapy, and should be able to liaise closely is always possible, even if rare in children [10]. with other physicians involved in managing the patient. Therefore, we recommend that in these patients, the Children undergoing 131I-mIBG therapy should be diagnostic scintigraphy and the therapeutic administra- managed jointly by teams including the specialist paediatric tion of mIBG are conducted without changing the staff [8]. medication taken, although using beta blockers or Clinicians involved in unsealed source therapy must be calcium channels blockers could impair the efficacy of knowledgeable about and compliant with all applicable procedure. In the other patients, a slow administration of national and local legislation and regulations. the mIBG, which should be stopped if hypertension occurs, is recommended (see “Administration”). Patient preparation and data required 1. Patients should have a proven, inoperable neuro-endocrine tumour and have undergone conventional staging inves- Patient information and instruction tigations including mIBG scintigraphy, anatomical imag- ing (CT, MRI, ultrasound) and biochemical assessment to Patients should receive both written and verbal information identify objective tumour markers. about the procedure before receiving therapy. If necessary, 2. Eligible patients will have mIBG-positive tumours, informed written consent must be obtained from the patient documented by tracer scintigraphy using 123I-mIBG as [11]. a diagnostic tracer (in adults, 131I-mIBG can also be used After appropriate guidance, comforters and carers may for tumour imaging). be encouraged to participate in the care of children 3. Thyroidal uptake of free iodide is prevented using per undergoing mIBG therapy, especially in case of small oral stable iodine (Table 1) Capsules of oral iodine are children, depending on local regulations. Usually these more suitable for children because of their neutral taste. carers will be family members, i.e. parents and/or grand- The treatment should begin 48–24 h before the planned parents. If these carers are expected to receive a radiation mIBG administration and continued for 10–15 days post- burden exceeding the constraints of 1 mSv/year, an therapy. Potassium perchlorate, normally used alone informed consent should be obtained in accordance with before mIBG scintigraphy, is here generally used in the status of ‘willingly and knowingly exposed comforters combination with stable iodine to facilitate the wash-out and carers,’ and an annual constraint should be defined.