SNM Practice Guideline for Dopamine Transporter Imaging with 123I-Ioflupane SPECT 1.0*

SNM Practice Guideline for Dopamine Transporter Imaging with 123I-Ioflupane SPECT 1.0* David S.W. Djang1, Marcel J.R. Janssen2, Nicolaas Bohnen3, Jan Booij4, Theodore A. Henderson5, Karl Herholz6, Satoshi Minoshima7, Christopher C. Rowe8, Osama Sabri9, John Seibyl10, Bart N.M. Van Berckel11, and Michele Wanner12 1Seattle Nuclear Medicine, Seattle, Washington; 2Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 3University of Michigan Medical Center, Ann Arbor, Michigan; 4Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 5The Synaptic Space, Centennial, Colorado; 6Wolfson Molecular Imaging Centre, Manchester, England; 7University of Washington, Seattle, Washington; 8Austin Hospital, Melbourne, Australia; 9University Hospital Leipzig, Leipzig, Saxony, Germany; 10Institute for Neurodegenerative Disorders, New Haven, Connecticut; 11VU University Medical Center Amsterdam, Amsterdam, The Netherlands; and 12University of Washington, Seattle, Washington tion of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to PREAMBLE assist practitioners in providing appropriate care for The Society of Nuclear Medicine (SNM) is an interna- patients. They are not inflexible rules or requirements of tional scientific and professional organization founded in practice and are not intended, nor should they be used, to 1954 to promote the science, technology, and practical establish a legal standard of care. For these reasons and application of nuclear medicine. Its 16,000 members are those set forth below, the SNM cautions against the use of physicians, technologists, and scientists specializing in the these guidelines in litigation in which the clinical decisions research and practice of nuclear medicine. In addition to of a practitioner are called into question. publishing journals, newsletters, and books, the SNM also The ultimate judgment regarding the propriety of any sponsors international meetings and workshops designed to specific procedure or course of action must be made by the increase the competencies of nuclear medicine practitioners physician or medical physicist in light of all the circum- and to promote new advances in the science of nuclear stances presented. Thus, there is no implication that an medicine. approach differing from the guidelines, standing alone, was The SNM will periodically define new practice guidelines below the standard of care. To the contrary, a conscientious for nuclear medicine practice to help advance the science of practitioner may responsibly adopt a course of action nuclear medicine and to improve the quality of service to different from that set forth in the guidelines when, in the patients throughout the United States. Existing practice reasonable judgment of the practitioner, such course of guidelines will be reviewed for revision or renewal, as action is indicated by the condition of the patient, appropriate, on their fifth anniversary or sooner, if indicated. limitations of available resources, or advances in knowl- Each practice guideline, representing a policy statement edge or technology subsequent to publication of the guide- by the SNM, has undergone a thorough consensus process in which it has been subjected to extensive review, lines. requiring the approval of the Committee on Guidelines The practice of medicine involves not only the science, and SNM Board of Directors. The SNM recognizes that the but also the art, of dealing with the prevention, diagnosis, safe and effective use of diagnostic nuclear medicine alleviation, and treatment of disease. The variety and imaging requires specific training, skills, and techniques, complexity of human conditions make it impossible to as described in each document. Reproduction or modifica- always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful Received Nov. 11, 2011; accepted Nov. 11, 2011. outcome. All that should be expected is that the practitioner For correspondence or reprints contact David S.W. Djang, Seattle Nuclear Medicine, 1229 Madison St., Suite 1050, Seattle, WA 98104-1377. will follow a reasonable course of action based on current E-mail: [email protected] knowledge, available resources, and the needs of the patient *NOTE: YOU CAN ACCESS THIS GUIDELINE THROUGH THE SNM WEBSITE (http://www.snm.org/guidelines). to deliver effective and safe medical care. The sole purpose Published online Dec. 8, 2011. COPYRIGHT ª 2012 by the Society of Nuclear Medicine, Inc. of these guidelines is to assist practitioners in achieving this DOI: 10.2967/jnumed.111.100784 objective. 154 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 53 • No. 1 • January 2012 I. INTRODUCTION dopamine as the neurotransmitter. Dopamine is produced in N-v-fluoropropyl-2b-carbomethoxy-3b-(4-123I-iodo- the presynaptic nerve terminals and transported into vesicles phenyl)nortropane (123I-ioflupane) is a molecular imaging by the vesicular monoamine transporter 2 (an integral agent used to demonstrate the location and concentration of membrane protein that transports neurotransmitters such as dopamine transporters (DaTs) in the synapses (Fig. 1) of dopamine from the cytosol into vesicles). On excitation, the striatal dopaminergic neurons. This agent has shown effi- dopamine from these vesicles is released into the synapse and cacy for detecting degeneration of the dopaminergic nigro- binds to the predominantly postsynaptic dopamine receptors. striatal pathway, allowing better separation of patients with On the presynaptic side, DaTs move dopamine out of the essential tremor from those with presynaptic Parkinsonian synaptic cleft and back into the nigrostriatal nerve terminals syndromes, as well as differentiating between some causes for either storage or degradation. of parkinsonism. Imaging the integrity of the nigrostriatal dopaminergic Parkinsonian syndromes are a group of diseases that system can improve the accuracy of diagnosing movement share similar cardinal signs of parkinsonism, characterized disorders. DaT concentrations are lower in presynaptic by bradykinesia, rigidity, tremor at rest, and postural Parkinsonian syndromes, which include Parkinson’s disease, instability. Although the neurodegenerative condition Par- multiple system atrophy, and progressive supranuclear palsy, kinson’s disease is the most common cause of parkinson- and are also lower in dementia with Lewy bodies. In these ism, numerous other etiologies can lead to a similar set of cases, the decrease in DaT density is probably even greater symptoms, including multiple system atrophy, progressive than the decrease in intact synapses, due to compensatory supranuclear palsy, corticobasal degeneration, drug-in- downregulation of DaT in an attempt to increase synaptic duced parkinsonism, vascular parkinsonism, and psycho- dopamine concentrations. Conversely, DaT concentrations genic parkinsonism. Essential tremor typically occurs will generally be normal in parkinsonism without presynap- during voluntary movement rather than at rest; however, tic dopaminergic loss, which includes essential tremor, drug- some patients with essential tremor can demonstrate resting induced parkinsonism, and psychogenic parkinsonism. And tremor, rigidity, or other isolated Parkinsonian features, in contrast to dementia with Lewy bodies, DaT concentra- mimicking other etiologies. Clinical diagnosis of parkin- tions are usually normal in Alzheimer’s disease (3–18). sonism is often straightforward, obviating additional tests Anatomic imaging is of little help when determining the in many cases. However, for incomplete syndromes, or an integrity of this system, but both presynaptic and postsynaptic overlap between multiple concurrent conditions, particu- levels can be targeted by PET and SPECT tracers. There are 18 larly early on, an improvement in diagnostic accuracy several PET tracers (e.g., F-dihydroxyphenylalanine for L- 11 may be possible using a test for DaT visualization (1–3). dihydroxyphenylalanine decarboxylase activity; C-dihydro- The dopaminergic neurotransmitter system plays a vital tetrabenazine for vesicular monoamine transporter 2), but role in parkinsonism. The nigrostriatal dopaminergic pathway their use is limited primarily to scientific research. For can be analyzed at the striatal level, where the nigrostriatal SPECT, most tracers are cocaine analogs and target DaT 123 123 neurons end and connect to the postsynaptic neurons using (19,20). One such tracer is I-iometopane ( I-b-CIT), available largely for research (21). Similar in chemical struc- ture, 123I-ioflupane (123I-FP-CIT) is a SPECT tracer, licensed by the European Medicines Agency and available in Europe since 2000. In the United States, 123I-ioflupane was approved by the Food and Drug Administration on January 2011 and is commercially available (22). This guideline covers the indi- cations, technical aspects, interpretation, and reporting of DaT SPECT scans with 123I-ioflupane and considers the work of the European Association of Nuclear Medicine (23). II. GOALS The purpose of this information is to assist health care professionals in performing, interpreting, and reporting the results of DaT imaging with 123I-ioflupane SPECT. III. DEFINITIONS See also the SNM Guideline for General Imaging. 123I-ioflupane is the nonproprietary name for N-v-fluoropropyl-2b-carbomethoxy-3b-(4-123I-iodophenyl)nortropane,

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