Nuclear Medicine and Diagnostic Imaging (NMDI)
Programme Activities of the IAEA's Sub-Programme on Nuclear Medicine
The objective of the sub-programme on Nuclear Medicine is to enhance the capabilities of Member States to address major health problems, like cancer and cardiovascular disease, effectively and efficiently using nuclear medicine techniques when appropriate and in a cost-effective manner. This goal will be achieved by raising Nuclear Medicine practice standards by providing targeted education and training; assisting in establishing new practices; transferring updated technology and implementing appropriate, clinically relevant and updated diagnostic and therapeutic applications.
The subprogramme consists of five main projects, namely:
Improvement of secondary prevention in ischemic heart disease through strengthening the use of nuclear cardiology techniques
Rationale: Cardiovascular disease (CVD) refers to a class of diseases that involves the heart and/or blood vessels. While the term technically refers to any disease that affects the cardiovascular system, it is generally used to identify conditions related to atherosclerosis. Atherosclerosis is a process that develops over decades and is silent in a large proportion of cases until an acute and sometimes fatal event (such as a heart attack, sudden death or a stroke) occurs, usually at or after the fourth decade of life. There is frequently a misconception that cancer kills more than CVD, especially breast cancer in women, however statistics show the opposite. According to the World Health Organization (WHO), CVD is the leading cause of mortality in adults worldwide for both men and women, killing a larger number of individuals as compared to cancer. It is estimated that currently 17.5 million people die every year due to CVD, which corresponds to about 30% of all causes of deaths in the world. Unfortunately, if this trend continues, by the year 2015 this number will increase to approximately 20 million global deaths per year, of which between 7 and 8.5 million people will be under the age of 70. Of major importance is that WHO estimated that 80% of all these deaths occur in low to middle income countries (developing nations) with limited resources to face a problem of this magnitude.
Affected victims of this condition are usually at their peak productive years in life, which further aggravates the economic problems of these needy nations. Clinical care of coronary artery disease (CAD) is costly and prolonged. Because of these direct costs scarce family and societal resources are diverted to medical care. CAD affects individuals in their peak mid life years jeopardizing the future of the families dependent on them and undermining the development of nations by depriving valuable human resources in their most productive years.
Nuclear Cardiology is a well established technique to detect coronary artery disease and to assess left ventricular function. A radiotracer is injected to the patient and images are obtained using a special instrument (gamma camera). In the United States of America and Canada as well as in other developed countries, this is the most commonly used method for detecting and determining the severity of coronary artery disease. It is sensitive, accurate and cost-effective and gives excellent prognostic information that is not provided by other diagnostic modalities.
Nuclear cardiology procedures, in particular myocardial perfusion studies (MPS) are cost-effective in several settings because they are mostly outpatient investigations of moderate cost, high diagnostic accuracy and low risk. This is an important issue of particular interest to developing countries with limited resources to be allocated to the health area. For example, in patients with stable angina and intermediate pre-test probability of CAD, it has been shown that a diagnostic strategy guided by MPS is more cost effective than a strategy using direct coronary angiography or computed tomography (CT) angiography. A MPS-led management strategy results in 23–41% cost-savings compared with direct referral to coronary angiography. Therefore, and contrary to wide-spread popular opinion, MPS is a costsaving procedure in the overall management of chronic CAD patients.
The aim of this project is to disseminate information on the clinical value of nuclear medicine procedures, specifically in those conditions which would most benefit from its application and to provide support to human resources capacity building.
- To enhance the effective use of appropriate nuclear cardiology procedures in Member States through Agency support.
Clinical PET/CT, molecular imaging and multimodality approach in diagnosis and control of disease
Rationale: Growing global population, increased ageing of the population, chronically ill people and increasing awareness and need for medical services are all driving the growth of the medical imaging market even in developingcountries. During the past decade, medical imaging has experienced substantial developments, mostly after the introduction of positron emission tomography (PET) in clinical practice. PET, and particularly PET/CT, has recently been recognized not only as an important research instrument, but also as a reliable imaging tool for diagnosing and staging of disease, as well as for therapeutic planning and the monitoring/evaluation of response to therapeutic interventions. Accurate anatomical localization of functional abnormalities obtained with the use of PET is known to be problematic. Although tracers such as 18F-fluoro-deoxy-glucose (18F-FDG) permit visualization of certain normal anatomical structures, the spatial resolution is generally inadequate for accurate anatomic localization of pathology.
Combining PET with a high-resolution anatomical imaging modality such as computed tomography (CT) can resolve the localization issue as long as the images from the two modalities are accurately coregistered. That is also true for single photon emission computed tomography (SPECT) using conventional radiopharmaceuticals. Like PET/CT, SPECT/CT acquires both scans with the patient in the same position. Grafting the high spatial resolution capabilities of today’s high-speed CT scanners with PET and SPECT allows for highly accurate definition of disease processes vastly enhancing anatomical mapping and localization, moving the new hybrid technology directly into a wider range of clinical applications. Most significantly, CT attenuation correction greatly reduces the problems of distortion and degradation that typically occur with radionuclide-based methods.
Many organic substances can be labelled with positron emitters like C-11, N-13, F-18 or O-15 without altering their physiological properties. Of these, F-18 fluoro-deoxy-glucose (F-18 FDG) is the most commonly applied tracer but other pharmaceuticals labelled with F-18 are being developed as well. Thus, metabolic information, such as the changes in regional distribution of glucose, fatty acids or amino acids can be determined. This information can be applied to kinetic models to translate the regional concentrations in the image in order to assess physiological and metabolic processes. The technique has been found to be useful in oncology for diagnosing and staging of many tumour types and to evaluate therapeutic effects. For cancer, the introduction of PET has made a critical contribution to the accurate definition of clinical stage at presentation and the accurate assessment of disease clearance at the end of treatment.
An area as fast growing as diagnostic imaging, and more specifically diagnostic radiology, is Computed Tomography (CT), which plays a crucial role in cancer control and management. Without medical imaging diagnostic tools such as CT, and wherever affordable PET/CT, the implementation of cancer control programs through PACT will not meet the standard of practice of clinical oncology. Indeed, CT is an imaging modality that is already part of many current projects in radiotherapy and nuclear medicine. Therefore, NAHU should be prepared to address clinical and radiation protection issues caused by the increasing use of CT in developing countries.
Web based tools for education, databases and quality management for professional development
Rationale: Professional standards and quality management (QM) of nuclear medicine services are intractably linked. Good clinical governance, risk reduction strategies and optimized utilization of all resources are essential to modern day practices. Given the complexity and multidisciplinary nature of the processes involved in nuclear medicine practices, quality management is essential for achieving the goals of nuclear medicine imaging. The maintenance of the NUMDAB database is essential starting point for quality management audits.
Quality assurance implies that the optimization of all aspects of a given process is guaranteed by a series of steps, which can be globally defined as quality management. Quality management systems are maintained with the intention of continuously improving effectiveness and efficiency, enabling nuclear medicine to achieve the expectations of its Quality policy, and satisfy its customers. All aspects of nuclear medicine, or molecular imaging, should be guided by quality goals and Quality management as the way to achieving this. Ideally, this process should lead towards accreditation which is increasingly a central requirement for quality in the health sector.
Trained human resources are a key element in quality systems, therefore professional development and web based educational support is essential. Web-based tools provide easy access and immediate information to assist with professional development. What the Agency web based tools uniquely provide, is a balance between knowledge based activities and sharing of experience. Nuclear physicians, technologists, radiographers, medical physicists, and radiopharmacists are all increasingly required to provide evidence of continuing professional activities for their respective practice licences. Although there is considerable information available however, tailoring this to objectives of the Agency’s subprogramme in nuclear medicine is essential. This project activity is essential for sustaining the future growth of Quality management systems in nuclear medicine Members States.
- To establish web based tools for multidisciplinary approach to e-learning for continuing professional development.
- To assist Member States to establish quality management systems in nuclear medicine and raise the standards of clinical practice.
Cost-effective radiopharmaceuticals: Clinical applications (complementary project to radioisotope production and radiation technology project 188.8.131.52)
Rationale: Molecular understanding and new therapeutics are beginning to make a real difference in terms of survival and improvement in the quality of life. At an international level the availability of safe, efficacious and quality modern radiopharmaceuticals for diagnosis and treatment of major diseases remain a real challenge. Hence it is extremely important to address challenges of production, product approvals, logistics and cost effective clinical utility of therapeutic radiopharmaceuticals at affordable prices to the nuclear medicine community in developing countries.
The development of PET/CT and related technologies is revolutionising diagnostic work up of patients in nuclear medicine. However there is a need for better strategies for radiopharmaceutical products (RP) at affordable prices. Helping the Member States to develop capacity to produce radiopharmaceuticals at local production costs is important. The generator based developments including radio-nuclide based therapies can make significant differences. Further there is a need to develop the role of centralized radiopharmacies with a view to creating specialist centres which are more responsive to local clinical demands. In addition there is a need to strengthen access and quality programmes. The recent publications of key IAEA guidance documents and a chapter of radiopharmaceuticals in WHO International pharmacopoeia provide an ideal opportunity for promoting standards of practice for radiopharmaceutical activities both at industrial and hospital radiopharmacy level. Many new radiopharmaceuticals still have great difficulties going from bench to clinics. There is need for ensuring international standards and efficient supply of radiopharmaceuticals. The internationally based WHO-Agency prequalification programme which is systematic and transparent will fast-track radiopharmaceutical approval and ensure that only qualitative, safe and efficacious radiopharmaceuticals reach the clinics. Web based information will enable nuclear physicians and authorities to recognize approved products therefore reducing the risk of using regulatory exemption schemes with unregistered products, manufacturers and suppliers.
In summary, this project addresses the needs for effective translational research transfer, indigenous production, faster approval mechanisms, and good manufacturing practice of radiopharmaceuticals into clinical practice.
Projects in Programmes 2.2 (Human Health) and in 2.5 (Radioisotope Production and Radiation technology) will, through coordinated activities, jointly address these developmental and usage issues.
- To facilitate effective translational research on newer techniques for routine use in nuclear medicine facilities in Member States including and production of affordable therapeutic radiopharmaceutical products, in particular alpha- and beta-emitters for targeted therapy.
- To widen systems that promote greater safety culture by application of internationally prepared documents and standards, radiopharmaceutical approvals, and quality management in production of radiopharmaceuticals (good manufacturing practice (GMP); GCP; QA/QC).
- To help Member States in the assimilation of new technologies, and training for staff in hospital ‘hot’ laboratories.
Molecular targeted radiopharmaceuticals for diagnosis and therapy in noncommunicable diseases
Rationale: The molecular characterization of cancer at the individual level by means of oncogene or receptor profiling, angiogenesis, drug resistance, tumour hypoxia, proliferation and tumour metabolism have significantly impacted treatment design and is expected to improve cancer patients’ survival. In recent years, a number of new developments in targeted therapies using radiolabelled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumours with radiolabelled monoclonal antibodies (mAbs), the developments in the application of radiolabelled small receptor-specific molecules such as metaiodobenzylguanidine and peptides, and the position of locoregional treatment in malignant involvement of the liver are expanding as well as the concept of combining therapeutic radiopharmaceuticals with other treatment modalities are being more extensively explored.
Modern targeted-therapy options applying “intelligent” radiopharmaceuticals or non-radioactive targeted molecules in combination with other treatment modalities have led to improved survival and quality of life of patients with several types of cancer. Major developments in this field comprise the routine use of radiolabelled anti-CD20 monoclonal antibodies for lymphoma and radiolabelled peptides especially for neuro-endocrine tumours.
Within the framework of improving the clinical efficacy of targeted radionuclide treatment, the prescription of an individualized irradiation dose to critical organs is a concept that has been promoted by several leading centres. Dosimetric data is gathered to predict the dose to the critical organ by injecting the same radiopharmaceutical as a “tracer activity”. For imaging purposes and metabolic or receptor profiling of cancer the same molecules can be tagged with positron emitters (F-18, Ga-68, Y-86, I-124) or single photon emitters (Tc-99m, In-111 I-131or I-123) to provide diagnostic information.
Therapeutic applications in nuclear medicine are effective in treating specific disease conditions as thyrotoxicosis, rheumatoid and haemophilic joints disease, and in malignancy as in thyroid cancer, lymphomas and disseminated metastatic conditions to the bone and other organs with excellent tolerability and minor side effects. In most instances these diagnostic and therapeutic approaches are cost-effective too. As in any medical specialty, the introduction of new diagnostic or treatment protocols, comprising novel radiopharmaceuticals, calls upon disseminating specialized expert knowledge, skills and continuing education to assure their successful implementation in clinical routine. Nuclear Medicine imaging techniques are playing an important role for the diagnosis of dementing and non-dementing neurodegenerative disease and in the diagnosis of epilepsy. Along with genomic research, the development of novel and more effective drugs establishing an accurate diagnosis early on in the disease has become a crucial event in the chain leading to an appreciable slowing disease progression in disorders causing dementia and or debilitating movement disorders. The accessibility of many developing Member States to both therapeutic application and diagnostic techniques is limited for a variety of reasons. Only few developing states govern the know-how, possess appropriate infrastructure, equipment and properly trained personnel to provide sustainable high quality services in these fields. The Agency has been involved in addressing the special needs of Member States tailored to the local needs and specific spectrum of prevalent diseases, by creating sustainable national and regional capacities for the production of clinically suitable, cost effective radioisotopes and radio-pharmaceuticals and to tackle the medical needs through implementing novel therapeutic and diagnostic techniques. Furthermore, the Agency remains engaged in developing human capabilities in more advanced diagnostic and therapeutic Nuclear Medicine applications of which some have received world-wide acclaim.
- To develop, evaluate and introduce diagnostic and therapeutic radiopharmaceuticals and correspondingimaging and treatment procedures.